Abstract
Cancer is the result of disturbed cell functions. Cancer is induced by the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which then leads to genetic instability. Chemotherapy is a major option to treat cancer, yet classical treatments induce toxic effects. Alternatively, cancer nanomedicines with tumor-targeted properties are very promising for improved safety and efficacy. Nanomedicines are sub-micrometer formulations designed to improve the biodistribution of anticancer drugs, resulting in modified toxicity, less off-target localization, enhanced efficacy and improved accumulation at the target site. For designing a targeted nanodrug system, the pathophysiological characteristics of tumors should be studied. This article explains how to make smart nanomedicines based on tumor-associated pathological features. Advantages include selective cell uptake, better drug release, increased therapeutic efficiency, receptor-mediated cell endocytosis, enhanced permeability and retention, and reduced systemic effects.
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Abdollahpour-Alitappeh M, Lotfinia M, Gharibi T, Mardaneh J, Farhadihosseinabadi B, Larki P et al (2019) Antibody-drug conjugates (ADCs) for cancer therapy: strategies, challenges, and successes. J Cell Physiol 234:5628–5642. https://doi.org/10.1002/jcp.27419
Ahn J, Miura Y, Yamada N, Chida T, Liu X, Kim A et al (2015) Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer. Biomaterials 39:23–30. https://doi.org/10.1016/j.biomaterials.2014.10.069
Ai J, Biazar E, Jafarpour M, Montazeri M, Majdi A, Aminifard S et al (2011) Nanotoxicology and nanoparticle safety in biomedical designs. Int J Nanomed 6:1117–1127. https://doi.org/10.2147/IJN.S16603
Akkapeddi P, Azizi SA, Freedy AM, Pmsd Cal, Gois PMP et al (2016) Construction of homogeneous antibody-drug conjugates using site-selective protein chemistry. Chem Sci 7:2954–2963. https://doi.org/10.1039/c6sc00170j
Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515. https://doi.org/10.1021/mp800051m
Anselmo AC, Mitragotri S (2016) Nanoparticles in the clinic. Bioeng Transl Med 1:10–29. https://doi.org/10.1002/btm2.10003
Aquib M, Farooq MA, Banerjee P, Akhtar F, Filli MS, Boakye-Yiadom KO (2019) Targeted and stimuli–responsive mesoporous silica nanoparticles for drug delivery and theranostic use. J Biomed Mater Res A 107:2643–2666. https://doi.org/10.1002/jbm.a.36770
Arabi L, Badiee A, Mosaffa F, Jaafari MR (2015) Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin. J Control Release 220:275–286. https://doi.org/10.1016/j.jconrel.2015.10.044
Ballabh P, Braun A, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16:1–13. https://doi.org/10.1016/j.nbd.2003.12.016
Battigelli A, Russier J, Venturelli E, Fabbro C, Petronilli V, Bernardi P et al (2013) Peptide-based carbon nanotubes for mitochondrial targeting. Nanoscale 5:9110–9117. https://doi.org/10.1039/c3nr02694a
Bavi R, Liu Z, Han Z, Zhang H, Gu Y (2019) In silico designed RNA aptamer against epithelial cell adhesion molecule for cancer cell imaging. Biochem Biophys Res Commun 509:937–942. https://doi.org/10.1016/j.bbrc.2019.01.028
Boogerd LS, Boonstra MC, Beck AJ, Charehbili A, Hoogstins CE, Prevoo HA et al (2016) Concordance of folate receptor-alpha expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients. Oncotarget 7:17442–17454. https://doi.org/10.18632/oncotarget.7856
Callmann CE, Barback CV, Thompson MP, Hall DJ, Mattrey RF, Gianneschi NC (2015) Therapeutic enzyme-responsive nanoparticles for targeted delivery and accumulation in tumors. Adv Mater 27:4611–4615. https://doi.org/10.1002/adma.201501803
Cao Y, Li Y, Hu XY, Zou X, Xiong S, Lin C et al (2015) Supramolecular nanoparticles constructed by DOX-based prodrug with water-soluble pillar [6] arene for self-catalyzed rapid drug release. Chem Mater 27:1110–1119. https://doi.org/10.1021/cm504445r
Chamundeeswari M, Jeslin J, Verma ML (2019) Nanocarriers for drug delivery applications. Environ Chem Lett 17:849–865. https://doi.org/10.1007/s10311-018-00841-1
Chen JX, Wang HY, Li C, Han K, Zhang XZ, Zhuo RX (2011) Construction of surfactant-like tetra-tail amphiphilic peptide with RGD ligand for encapsulation of porphyrin for photodynamic therapy. Biomaterials 32:1678–1684. https://doi.org/10.1016/j.biomaterials.2010.10.047
Chen JX, Xu XD, Chen WH, Zhang XZ (2014) Multi-functional envelope-type nanoparticles assembled from amphiphilic peptidic prodrug with improved anti-tumor activity. ACS Appl Mater Interfaces 6:593–598. https://doi.org/10.1021/am404680n
Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y et al (2015a) New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med 13:45. https://doi.org/10.1186/s12916-015-0278-7
Chen WH, Luo GF, Lei Q, Jia HZ, Hong S, Wang QR et al (2015b) MMP-2 responsive polymeric micelles for cancer-targeted intracellular drug delivery. Chem Commun (Camb) 51:465–468. https://doi.org/10.1039/c4cc07563c
Chen W, Zou Y, Zhong Z, Haag R (2017a) Cyclo(RGD)-decorated reduction-responsive nanogels mediate targeted chemotherapy of integrin overexpressing human glioblastoma in vivo. Small 13:6. https://doi.org/10.1002/smll.201601997
Chen WH, Luo GF, Lei Q, Hong S, Qiu WX, Liu LH et al (2017b) Overcoming the heat endurance of tumor cells by interfering with the anaerobic glycolysis metabolism for improved photothermal therapy. ACS Nano 11:1419–1431. https://doi.org/10.1021/acsnano.6b06658
Chen WH, Luo GF, Qiu WX, Lei Q, Liu LH, Wang SB et al (2017c) Mesoporous silica-based versatile theranostic nanoplatform constructed by layer-by-layer assembly for excellent photodynamic/chemo therapy. Biomaterials 117:54–65. https://doi.org/10.1016/j.biomaterials.2016.11.057
Chen D, Tang Q, Zou J, Yang X, Huang W, Zhang Q et al (2018) pH-responsive PEG-doxorubicin-encapsulated Aza-BODIPY nanotheranostic agent for imaging-guided synergistic cancer therapy. Adv Healthc Mater 7:e1701272. https://doi.org/10.1002/adhm.201701272
Cheng H, Zhu JY, Xu XD, Qiu WX, Lei Q, Han K et al (2015) Activable cell-penetrating peptide conjugated prodrug for tumor targeted drug delivery. ACS Appl Mater Interfaces 7:16061–16069. https://doi.org/10.1021/acsami.5b04517
Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668. https://doi.org/10.1021/nl052396o
Chudasama V, Maruani A, Caddick S (2016) Recent advances in the construction of antibody-drug conjugates. Nat Chem 8:114–119. https://doi.org/10.1038/nchem.2415
Coney LR, Tomassetti A, Carayannopoulos L, Frasca V, Kamen BA, Colnaghi MI et al (1991) Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res 51:6125–6132
Cui Y, Xu Q, Chow PK, Wang D, Wang CH (2013) Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 34:8511–8520. https://doi.org/10.1016/j.biomaterials.2013.07.075
Daneman R, Prat A (2015) The blood-brain barrier. Cold Spring Harb Perspect Biol 7:a020412. https://doi.org/10.1101/cshperspect.a020412
Danhier F, Le Breton A, Preat V (2012) RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Mol Pharm 9:2961–2973. https://doi.org/10.1021/mp3002733
Daniels TR, Delgado T, Rodriguez JA, Helguera G, Penichet ML (2006) The transferrin receptor part I: biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol 121:144–158. https://doi.org/10.1016/j.clim.2006.06.010
Du C, Deng D, Shan L, Wan S, Cao J, Tian J et al (2013) A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery. Biomaterials 34:3087–3097. https://doi.org/10.1016/j.biomaterials.2013.01.041
Du JZ, Li HJ, Wang J (2018) Tumor-acidity-cleavable maleic acid amide (TACMAA): a powerful tool for designing smart nanoparticles to overcome delivery barriers in cancer nanomedicine. Acc Chem Res 51:2848–2856. https://doi.org/10.1021/acs.accounts.8b00195
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174. https://doi.org/10.1038/nrc745
Fan Y, Li C, Li F, Chen D (2016a) pH-activated size reduction of large compound nanoparticles for in vivo nucleus-targeted drug delivery. Biomaterials 85:30–39. https://doi.org/10.1016/j.biomaterials.2016.01.057
Fan Z, Sun L, Huang Y, Wang Y, Zhang M (2016b) Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release. Nat Nanotechnol 11:388–394. https://doi.org/10.1038/nnano.2015.312
Fan R, Mei L, Gao X, Wang Y, Xiang M, Zheng Y et al (2017a) Self-assembled bifunctional peptide as effective drug delivery vector with powerful antitumor activity. Adv Sci (Weinh) 4:1600285. https://doi.org/10.1002/advs.201600285
Fan X, Zhang W, Hu Z, Li Z (2017b) Facile synthesis of RGD-conjugated unimolecular micelles based on a polyester dendrimer for targeting drug delivery. J Mater Chem B 5:1062–1072. https://doi.org/10.1039/c6tb02234k
Fang T, Duarte JN, Ling J, Li Z, Guzman JS, Ploegh HL (2016) Structurally defined alphaMHC-II nanobody-drug conjugates: a therapeutic and imaging system for B-cell lymphoma. Angew Chem Int Ed Engl 55:2416–2420. https://doi.org/10.1002/anie.201509432
Farooq MA, Aquib M, Khan DH, Ghayas S, Ahsan A, Ijaz M et al (2019) Nanocarrier-mediated co-delivery systems for lung cancer therapy: recent developments and prospects. Environ Chem Lett 17:1565–1583. https://doi.org/10.1007/s10311-019-00897-7
Feynman RP (1960) There’s plenty of room at the bottom. California Institute of Technology, Engineering and Science magazine
Gao S, Lin H, Zhang H, Yao H, Chen Y, Shi J (2019) Nanocatalytic tumor therapy by biomimetic dual inorganic nanozyme-catalyzed cascade reaction. Adv Sci (Weinh) 6:1801733. https://doi.org/10.1002/advs.201801733
Gerlowski LE, Jain RK (1986) Microvascular permeability of normal and neoplastic tissues. Microvasc Res 31:288–305. https://doi.org/10.1016/0026-2862(86)90018-x
Godin B, Chiappini C, Srinivasan S, Alexander JF, Yokoi K, Ferrari M et al (2012) Discoidal porous silicon particles: fabrication and biodistribution in breast cancer bearing mice. Adv Funct Mater 22:4225–4235. https://doi.org/10.1002/adfm.201200869
Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ et al (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A 105:11613–11618. https://doi.org/10.1073/pnas.0801763105
Graziadio A, Zanda M, Frau S, Fleming IN, Musolino M, Dall’Angelo S et al (2016) NGR tumor-homing peptides: structural requirements for effective APN (CD13) Targeting. Bioconjug Chem 27:1332–1340. https://doi.org/10.1021/acs.bioconjchem.6b00136
Grodzinski P, Kircher M, Goldberg M, Gabizon A (2019) Integrating nanotechnology into cancer care. ACS Nano 13:7370–7376. https://doi.org/10.1021/acsnano.9b04266
Gupta PK (2016) Fundamentals of toxicology: essential concepts and applications. Academic Press
Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG et al (2004) Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 10:7063–7070. https://doi.org/10.1158/1078-0432.CCR-04-0789
Han K, Wang SB, Lei Q, Zhu JY, Zhang XZ (2015a) Ratiometric biosensor for aggregation-induced emission-guided precise photodynamic therapy. ACS Nano 9:10268–10277. https://doi.org/10.1021/acsnano.5b04243
Han SS, Li ZY, Zhu JY, Han K, Zeng ZY, Hong W et al (2015b) Dual-pH sensitive charge-reversal polypeptide micelles for tumor-triggered targeting uptake and nuclear drug delivery. Small 11:2543–2554. https://doi.org/10.1002/smll.201402865
Han K, Zhang WY, Zhang J, Lei Q, Wang SB, Liu JW et al (2016) Acidity triggered tumor targeted chimeric peptide for enhanced intra nuclear photodynamic therapy. Adv Func Mater 26:4351–4361. https://doi.org/10.1002/adfm.201600170
He Y, Nie Y, Cheng G, Xie L, Shen Y, Gu Z (2014) Viral mimicking ternary polyplexes: a reduction-controlled hierarchical unpacking vector for gene delivery. Adv Mater 26:1534–1540. https://doi.org/10.1002/adma.201304592
He D, He X, Wang K, Yang X, Yang X, Zou Z et al (2015) Redox-responsive degradable honeycomb manganese oxide nanostructures as effective nanocarriers for intracellular glutathione-triggered drug release. Chem Commun (Camb) 51:776–779. https://doi.org/10.1039/c4cc08172b
Hu YW, Du YZ, Liu N, Liu X, Meng TT, Cheng BL et al (2015) Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. J Control Release 206:91–100. https://doi.org/10.1016/j.jconrel.2015.03.018
Hu JJ, Xiao D, Zhang XZ (2016) Advances in peptide functionalization on mesoporous silica nanoparticles for controlled drug release. Small 12:3344–3359. https://doi.org/10.1002/smll.201600325
Huang L, Zhang Q, Dai L, Shen X, Chen W, Cai K (2017) Phenylboronic acid-modified hollow silica nanoparticles for dual-responsive delivery of doxorubicin for targeted tumor therapy. Regen Biomater 4:111–124. https://doi.org/10.1093/rb/rbw045
Iravani S, Varma RS (2020) Green synthesis, biomedical and biotechnological applications of carbon and graphene quantum dots: a review. Environ Chem Lett 18:703–727. https://doi.org/10.1007/s10311-020-00984-0
Iyer AK, Khaled G, Fang J, Maeda H (2006) Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today 11:812–818. https://doi.org/10.1016/j.drudis.2006.07.005
Janib SM, Moses AS, MacKay JA (2010) Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev 62:1052–1063. https://doi.org/10.1016/j.addr.2010.08.004
Jiang W, Kim BY, Rutka JT, Chan WC (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 3:145–150. https://doi.org/10.1038/nnano.2008.30
Jiang S, Wang X, Zhang Z, Sun L, Pu Y, Yao H et al (2016) CD20 monoclonal antibody targeted nanoscale drug delivery system for doxorubicin chemotherapy: an in vitro study of cell lysis of CD20-positive Raji cells. Int J Nanomedicine 11:5505–5518. https://doi.org/10.2147/IJN.S115428
Jin E, Zhang B, Sun X, Zhou Z, Ma X, Sun Q (2013) Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery. J Am Chem Soc 135:933–940. https://doi.org/10.1021/ja311180x
Johansen A, Hansen HD, Svarer C, Lehel S, Leth-Petersen S, Kristensen JL et al (2018) The importance of small polar radiometabolites in molecular neuroimaging: a PET study with [(11)C]Cimbi-36 labeled in two positions. J Cereb Blood Flow Metab 38:659–668. https://doi.org/10.1177/0271678X17746179
Kalafatovic D, Nobis M, Son J, Anderson KI, Ulijn RV (2016) MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. Biomaterials 98:192–202. https://doi.org/10.1016/j.biomaterials.2016.04.039
Kamaly N, He JC, Ausiello DA, Farokhzad OC (2016) Nanomedicines for renal disease: current status and future applications. Nat Rev Nephrol 12:738–753. https://doi.org/10.1038/nrneph.2016.156
Kang Y, Ju X, Ding LS, Zhang S, Li BJ (2017) Reactive oxygen species and glutathione dual redox-responsive supramolecular assemblies with controllable release capability. ACS Appl Mater Interfaces 9(5):4475–4484. https://doi.org/10.1021/acsami.6b14640
Karimi M, Ghasemi A, Sahandi Zangabad P, Rahighi R, Moosavi Basri SM, Mirshekari H et al (2016) Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem Soc Rev 45:1457–1501. https://doi.org/10.1039/c5cs00798d
Kern JC, Cancilla M, Dooney D, Kwasnjuk K, Zhang R, Beaumont M et al (2016) Discovery of pyrophosphate diesters as tunable, soluble, and bioorthogonal linkers for site-specific antibody–drug conjugates. J Am Chem Soc 138:1430–1445. https://doi.org/10.1021/jacs.5b12547
Kolakowski RV, Haelsig KT, Emmerton KK, Leiske CI, Miyamoto JB, Cochran JH et al (2016) The methylene alkoxy carbamate self-immolative unit: utilization for the targeted delivery of alcohol-containing payloads with antibody-drug conjugates. Angew Chem Int Ed Engl 55:7948–7951. https://doi.org/10.1002/anie.201601506
Kolosenko I, Avnet S, Baldini N, Viklund J, De Milito A (2017) Therapeutic implications of tumor interstitial acidification. Semin Cancer Biol 43:119–133. https://doi.org/10.1016/j.semcancer.2017.01.008
Lammers T, Kiessling F, Hennink WE, Storm G (2010) Nanotheranostics and image-guided drug delivery: current concepts and future directions. Mol Pharm 7:1899–1912. https://doi.org/10.1021/mp100228v
Lee JW, Lu JY, Low PS, Fuchs PL (2002) Synthesis and evaluation of taxol-folic acid conjugates as targeted antineoplastics. Bioorg Med Chem 10:2397–2414. https://doi.org/10.1016/s0968-0896(02)00019-6
Lee MH, Kim JY, Han JH, Bhuniya S, Sessler JL, Kang C et al (2012) Direct fluorescence monitoring of the delivery and cellular uptake of a cancer-targeted RGD peptide-appended naphthalimide theragnostic prodrug. J Am Chem Soc 134:12668–12674. https://doi.org/10.1021/ja303998y
Lee BY, Li Z, Clemens DL, Dillon BJ, Hwang AA, Zink JI, Horwitz MA (2016) Redox-triggered release of moxifloxacin from mesoporous silica nanoparticles functionalized with disulfide snap-tops enhances efficacy against pneumonic tularemia in mice. Small 12(27):3690–3702. https://doi.org/10.1002/smll.201600892
Levengood MR, Zhang X, Hunter JH, Emmerton KK, Miyamoto JB, Lewis TS et al (2017) Orthogonal Cysteine Protection Enables Homogeneous Multi-Drug Antibody-Drug Conjugates. Angew Chem Int Ed Engl 56:733–737. https://doi.org/10.1002/anie.201608292
Li ZY, Liu Y, Wang XQ, Liu LH, Hu JJ, Luo GF et al (2013) One-pot construction of functional mesoporous silica nanoparticles for the tumor-acidity-activated synergistic chemotherapy of glioblastoma. ACS Appl Mater Interfaces 5:7995–8001. https://doi.org/10.1021/am402082d
Li SY, Liu LH, Jia HZ, Qiu WX, Rong L, Cheng H et al (2014a) A pH-responsive prodrug for real-time drug release monitoring and targeted cancer therapy. Chem Commun (Camb) 50:11852–11855. https://doi.org/10.1039/c4cc05008h
Li ZY, Liu Y, Hu JJ, Xu Q, Liu LH, Jia HZ et al (2014b) Stepwise-acid-active multifunctional mesoporous silica nanoparticles for tumor-specific nucleus-targeted drug delivery. ACS Appl Mater Interfaces 6:14568–14575. https://doi.org/10.1021/am503846p
Li F, Zhao X, Wang H, Zhao R, Ji T, Ren H et al (2015) Multiple layer by layer lipid polymer hybrid nanoparticles for improved FOLFIRINOX chemotherapy in pancreatic tumor models. Adv Func Mater 25:788–798. https://doi.org/10.1002/adfm.201401583
Li S, Amat D, Peng Z, Vanni S, Raskin S, De Angulo G et al (2016) Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. Nanoscale 8:16662–16669. https://doi.org/10.1039/c6nr05055g
Li SY, Cheng H, Qiu WX, Zhang L, Wan SS, Zeng JY, Zhang XZ (2017a) Cancer cell membrane-coated biomimetic platform for tumor targeted photodynamic therapy and hypoxia-amplified bioreductive therapy. Biomaterials 142:149–161. https://doi.org/10.1016/j.biomaterials.2017.07.026
Li Y, Lin J, Ma J, Song L, Lin H, Tang B et al (2017b) Methotrexate-camptothecin prodrug nanoassemblies as a versatile nanoplatform for biomodal imaging-guided self-active targeted and synergistic chemotherapy. ACS Appl Mater Interfaces 9:34650–34665. https://doi.org/10.1021/acsami.7b10027
Liang J, Wu WL, Xu XD, Zhuo RX, Zhang XZ (2014) pH responsive micelle self-assembled from a new amphiphilic peptide as anti-tumor drug carrier. Colloids Surf B Biointerfaces 114:398–403. https://doi.org/10.1016/j.colsurfb.2013.10.037
Liao WC, Sohn YS, Riutin M, Cecconello A, Parak WJ, Nechushtai R et al (2016) The application of stimuli responsive VEGF and ATP aptamer-based microcapsules for the controlled release of an anticancer drug, and the selective targeted cytotoxicity toward cancer cells. Adv Func Mater 26:4262–4273. https://doi.org/10.1002/adfm.201600069
Lim C, Won WR, Moon J, Sim T, Shin Y, Kim JC et al (2019) Co-delivery of d-(KLAKLAK) 2 peptide and doxorubicin using a pH-sensitive nanocarrier for synergistic anticancer treatment. J Mater Chem B 7:4299–4308. https://doi.org/10.1039/C9TB00741E
Liu J, Kolar C, Lawson TA, Gmeiner WH et al (2001) Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells. J Org Chem 66:5655–5663. https://doi.org/10.1021/jo005757n
Liu C, Qing Z, Zheng J, Deng L, Ma C, Li J et al (2015) DNA-templated in situ growth of silver nanoparticles on mesoporous silica nanospheres for smart intracellular GSH-controlled release. Chem Commun (Camb) 51:6544–6547. https://doi.org/10.1039/c5cc00557d
Liu J, Wei T, Zhao J, Huang Y, Deng H, Kumar A et al (2016) Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance. Biomaterials 91:44–56. https://doi.org/10.1016/j.biomaterials.2016.03.013
Liu JN, Bu W, Shi J (2017) Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia. Chem Rev 117:6160–6224. https://doi.org/10.1021/acs.chemrev.6b00525
Liu J, Dang H, Wang XW (2018) The significance of intertumor and intratumor heterogeneity in liver cancer. Exp Mol Med 50:e416. https://doi.org/10.1038/emm.2017.165
Lu S, Wang H, Sheng Y, Liu M, Chen P (2012) Molecular binding of self-assembling peptide EAK16-II with anticancer agent EPT and its implication in cancer cell inhibition. J Controlled Release 160:33–40. https://doi.org/10.1016/j.jconrel.2012.03.009
Mansur AA, de Carvalho SM, Mansur HS (2016) Bioengineered quantum dot/chitosan-tripeptide nanoconjugates for targeting the receptors of cancer cells. Int J Biol Macromol 82:780–789. https://doi.org/10.1016/j.ijbiomac.2015.10.047
Maruani A, Smith ME, Miranda E, Chester KA, Chudasama V, Caddick S (2015) A plug-and-play approach to antibody-based therapeutics via a chemoselective dual click strategy. Nat Commun 6:6645. https://doi.org/10.1038/ncomms7645
Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392
Meng HM, Liu H, Kuai H, Peng R, Mo L, Zhang XB (2016) Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy. Chem Soc Rev 45:2583–2602. https://doi.org/10.1039/c5cs00645g
Meric-Bernstam F, Johnson AM, Dumbrava EEI, Raghav K, Balaji K, Bhatt M et al (2019) Advances in HER2-targeted therapy: novel agents and opportunities beyond breast and gastric cancer. Clin Cancer Res 25:2033–2041. https://doi.org/10.1158/1078-0432.CCR-18-2275
Mo R, Jiang T, DiSanto R, Tai W, Gu Z (2014) ATP-triggered anticancer drug delivery. Nat Commun 5:3364. https://doi.org/10.1038/ncomms4364
Nasrollahi F, Varshosaz J, Khodadadi AA, Lim S, Jahanian-Najafabadi A (2016) Targeted Delivery of Docetaxel by Use of Transferrin/Poly(allylamine hydrochloride)-functionalized Graphene Oxide Nanocarrier. ACS Appl Mater Interfaces 8:13282–13293. https://doi.org/10.1021/acsami.6b02790
Natfji AA, Ravishankar D, Osborn HMI, Greco F (2017) Parameters Affecting the enhanced permeability and retention effect: the need for patient selection. J Pharm Sci 106:3179–3187. https://doi.org/10.1016/j.xphs.2017.06.019
Pan J, Lei S, Chang L, Wan D (2019) Smart pH-responsive nanoparticles in a model tumor microenvironment for enhanced cellular uptake. Mater Life Sci 54:1692–1702. https://doi.org/10.1007/s10853-018-2931-y
Paroha S, Chandel AKS, Dubey RD (2018) Nanosystems for drug delivery of coenzyme Q10. Environ Chem Lett 16:71–77. https://doi.org/10.1007/s10311-017-0664-9
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760. https://doi.org/10.1038/nnano.2007.387
Peng M, Qin S, Jia H, Zheng D, Rong L, Zhang X (2016) Self-delivery of a peptide-based prodrug for tumor-targeting therapy. Nano Res 9:663–673. https://doi.org/10.1007/s12274-015-0945-1
Peng F, Setyawati MI, Tee JK, Ding X, Wang J, Nga ME et al (2019) Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness. Nat Nanotechnol 14:279–286. https://doi.org/10.1038/s41565-018-0356-z
Petriev VM, Tischenko VK, Mikhailovskaya AA, Popov AA, Tselikov G, Zelepukin I et al (2019) Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of (188)Re radionuclide for cancer therapy. Sci Rep 9:2017. https://doi.org/10.1038/s41598-018-38474-7
Pierschbacher MD, Ruoslahti E (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309:30–33. https://doi.org/10.1038/309030a0
Qian ZM, Li H, Sun H, Ho K (2002) Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 54:561–587. https://doi.org/10.1124/pr.54.4.561
Qin SY, Feng J, Rong L, Jia HZ, Chen S, Liu XJ et al (2014) Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy. Small 10:599–608. https://doi.org/10.1002/smll.201301613
Qin SY, Peng MY, Rong L, Jia HZ, Chen S, Cheng SX et al (2015) An innovative pre-targeting strategy for tumor cell specific imaging and therapy. Nanoscale 7:14786–14793. https://doi.org/10.1039/c5nr03862f
Qin SY, Cheng YJ, Lei Q, Zhang AQ, Zhang XZ (2018a) Combinational strategy for high-performance cancer chemotherapy. Biomaterials 171:178–197. https://doi.org/10.1016/j.biomaterials.2018.04.027
Qin SY, Zhang AQ, Zhang XZ (2018b) Recent advances in targeted tumor chemotherapy based on smart nanomedicines. Small 14:e1802417. https://doi.org/10.1002/smll.201802417
Richards DA, Maruani A, Chudasama V (2017) Antibody fragments as nanoparticle targeting ligands: a step in the right direction. Chem Sci 8:63–77. https://doi.org/10.1039/c6sc02403c
Rodrigues T, Bernardes GJ (2016) Antibody–drug conjugates: the missing link. Nat Chem 8:1088–1090. https://doi.org/10.1038/nchem.2685
Roger E, Lagarce F, Garcion E, Benoit JP (2010) Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. Nanomedicine (Lond) 5:287–306. https://doi.org/10.2217/nnm.09.110
Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR (2019) Targeting tumor microenvironment for cancer therapy. Int J Mol Sci 20:4. https://doi.org/10.3390/ijms20040840
Rong L, Qin SY, Zhang C, Cheng YJ, Feng J, Wang SB (2018) Biomedical applications of functional peptides in nano-systems. Mater Today Chem 9:91–102. https://doi.org/10.1016/j.mtchem.2018.06.001
Rothan HA, Ambikabothy J, Ramasamy TS, Rashid NN, Yusof R (2019) A preliminary study in search of potential peptide candidates for a combinational therapy with cancer chemotherapy drug. Int J Pept Res Ther 25:115–122. https://doi.org/10.1007/s10989-017-9646-9
Schmidt MM, Wittrup KD (2009) A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol Cancer Ther 8:2861–2871. https://doi.org/10.1158/1535-7163.MCT-09-0195
Setyawati MI, Tay CY, Chia SL, Goh SL, Fang W, Neo MJ et al (2013) Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. Nat Commun 4:1673. https://doi.org/10.1038/ncomms2655
Setyawati MI, Mochalin VN, Leong DT (2016) Tuning endothelial permeability with functionalized nanodiamonds. ACS Nano 10:1170–1181. https://doi.org/10.1021/acsnano.5b06487
Setyawati MI, Tay CY, Bay BH, Leong DT (2017) Gold Nanoparticles induced endothelial leakiness depends on particle size and endothelial cell origin. ACS Nano 11:5020–5030. https://doi.org/10.1021/acsnano.7b01744
Shi H, Guo J, Li C, Wang Z (2015) A current review of folate receptor alpha as a potential tumor target in non-small-cell lung cancer. Drug Des Devel Ther 9:4989–4996. https://doi.org/10.2147/DDDT.S90670
Shi J, Wang B, Wang L, Lu T, Fu Y, Zhang H et al (2016) Fullerene (C60)-based tumor-targeting nanoparticles with “off-on” state for enhanced treatment of cancer. J Control Release 235:245–258. https://doi.org/10.1016/j.jconrel.2016.06.010
Singh R, Norret M, House MJ, Galabura Y, Bradshaw M, Ho D et al (2016) Dose-dependent therapeutic distinction between active and passive targeting revealed using transferrin-coated PGMA nanoparticles. Small 12:351–359. https://doi.org/10.1002/smll.201502730
Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516. https://doi.org/10.1146/annurev.cellbio.17.1.463
Stylianopoulos T, Poh MZ, Insin N, Bawendi MG, Fukumura D, Munn LL et al (2010) Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. Biophys J 99:1342–1349. https://doi.org/10.1016/j.bpj.20
Sumer B, Gao J (2008) Theranostic nanomedicine for cancer. Nanomedicine (Lond) 3:137–140. https://doi.org/10.2217/17435889.3.2.137
Sun Q, Bi H, Wang Z, Li C, Wang X, Xu J (2019) Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy. Biomaterials 223:119473. https://doi.org/10.1016/j.biomaterials.2019.119473
Tanaka A, Fukuoka Y, Morimoto Y, Honjo T, Koda D, Goto M et al (2015) Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator. J Am Chem Soc 137:770–775. https://doi.org/10.1021/ja510156v
Tang L, Tong R, Coyle VJ, Yin Q, Pondenis H, Borst LB (2015) Targeting tumor vasculature with aptamer-functionalized doxorubicin-polylactide nanoconjugates for enhanced cancer therapy. ACS Nano 9:5072–5081. https://doi.org/10.1021/acsnano.5b00166
Tang S, Meng Q, Sun H, Su J, Yin Q, Zhang Z et al (2017) Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer. Biomaterials 114:44–53. https://doi.org/10.1016/j.biomaterials.2016.06.005
Tao W, Zeng X, Wu J, Zhu X, Yu X, Zhang X et al (2016) Polydopamine-based surface modification of novel nanoparticle-aptamer bioconjugates for in vivo breast cancer targeting and enhanced therapeutic effects. Theranostics 6:470–484. https://doi.org/10.7150/thno.14184
Tay CY, Setyawati MI, Xie J, Parak WJ, Leong DT (2014) Back to basics: exploiting the innate physic chemical characteristics of nanomaterials for biomedical applications. Adv Func Mater 24:5936–5955. https://doi.org/10.1002/adfm.201401664
Tay CY, Setyawati MI, Leong DT (2017) Nanoparticle density: a critical biophysical regulator of endothelial permeability. ACS Nano 11:2764–2772. https://doi.org/10.1021/acsnano.6b07806
Toffoli G, Cernigoi C, Russo A, Gallo A, Bagnoli M, Boiocchi M (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198. https://doi.org/10.1002/(sici)1097-0215(19970422)74:2%3c193:aid-ijc10%3e3.0.co;2-f
Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4:528–539. https://doi.org/10.1038/nrc1391
Ulbrich K, Hola K, Subr V, Bakandritsos A, Tucek J, Zboril R (2016) Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies. Chem Rev 116:5338–5431. https://doi.org/10.1021/acs.chemrev.5b00589
Volkert WA, Hoffman TJ (1999) Therapeutic radiopharmaceuticals. Chem Rev 99:2269–2292. https://doi.org/10.1021/cr9804386
Wang HY, Chen JX, Sun YX, Deng JZ, Li C, Zhang XZ, Zhuo RX (2011) Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei. J Control Release 155:26–33. https://doi.org/10.1016/j.jconrel.2010.12.009
Wang Y, Yi S, Sun L, Huang Y, Lenaghan SC, Zhang M (2014) Doxorubicin-loaded cyclic peptide nanotube bundles overcome chemoresistance in breast cancer cells. J Biomed Nanotechnol 10:445–454. https://doi.org/10.1166/jbn.2014.1724
Wang J, Mao W, Lock LL, Tang J, Sui M, Sun W et al (2015a) The role of micelle size in tumor accumulation, penetration, and treatment. ACS Nano 9:7195–7206. https://doi.org/10.1021/acsnano.5b02017
Wang XG, Dong ZY, Cheng H, Wan SS, Chen WH, Zou MZ et al (2015b) A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy. Nanoscale 7:16061–16070. https://doi.org/10.1039/c5nr04045k
Wang HX, Zuo ZQ, Du JZ, Wang YC, Sun R, Cao ZT et al (2016) Surface charge critically affects tumor penetration and therapeutic efficacy of cancer nanomedicines. Nano Today 11:133–144. https://doi.org/10.1016/j.nantod.2016.04.008
Wang C, Wang J, Chen X, Zheng X, Xie Z, Chen L, Chen X (2017a) Phenylboronic acid-cross-linked nanoparticles with improved stability as dual acid-responsive drug carriers. Macromol Biosci 17:3. https://doi.org/10.1002/mabi.201600227
Wang H, Li Y, Bai H, Shen J, Chen X, Ping Y et al (2017b) A cooperative dimensional strategy for enhanced nucleus targeted delivery of anticancer drugs. Adv Func Mater 27:1700339. https://doi.org/10.1002/adfm.201700339
Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y et al (2017c) Role of tumor microenvironment in tumorigenesis. J Cancer 8:761–773. https://doi.org/10.7150/jca.17648
Wang J, Zhang L, Peng F, Shi X, Leong DT (2018) Targeting endothelial cell junctions with negatively charged gold nanoparticles. Chem Mater 30:3759–3767. https://doi.org/10.1021/acs.chemmater.8b00840
Webb BA, Chimenti M, Jacobson MP, Barber DL (2011) Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 11:671–677. https://doi.org/10.1038/nrc3110
Wei C, Zhang Y, Song Z, Xia Y, Xu H, Lang M (2017) Enhanced bioreduction-responsive biodegradable diselenide-containing poly(ester urethane) nanocarriers. Biomater Sci 5:669–677. https://doi.org/10.1039/c6bm00960c
Whatcott CJ, Han H, Posner RG, Hostetter G, Von Hoff DD (2011) Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov 1:291–296. https://doi.org/10.1158/2159-8290.CD-11-0136
Wibowo AS, Singh M, Reeder KM, Carter JJ, Kovach AR, Meng W et al (2013) Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci U S A 110:15180–15188. https://doi.org/10.1073/pnas.1308827110
Xiao D, Jia HZ, Zhang J, Liu CW, Zhuo RX, Zhang XZ (2014) A dual-responsive mesoporous silica nanoparticle for tumor-triggered targeting drug delivery. Small 10:591–598. https://doi.org/10.1002/smll.201301926
Yang Q, Wu L, Li L, Zhou Z, Huang Y (2017) Subcellular co-delivery of two different site-oriented payloads for tumor therapy. Nanoscale 9:1547–1558. https://doi.org/10.1039/c6nr08200a
Yao Y, Yu L, Su X, Wang Y, Li W, Wu Y (2015) Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates. J Control Release 220:5–17. https://doi.org/10.1016/j.jconrel.2015.09.058
Youn YS, Bae YH (2018) Perspectives on the past, present, and future of cancer nanomedicine. Adv Drug Deliv Rev 130:3–11. https://doi.org/10.1016/j.addr.2018.05.008
Zhai S, Hu X, Hu Y, Wu B, Xing D (2017) Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy. Biomaterials 121:41–54. https://doi.org/10.1016/j.biomaterials.2017.01.002
Zhang K, Li P, He Y, Bo X, Li X, Li D et al (2016) Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment. Biomaterials 99:34–46. https://doi.org/10.1016/j.biomaterials.2016.05.014
Zhang W, Lin W, Zheng X, He S, Xie Z (2017a) Comparing effects of redox sensitivity of organic nanoparticles to photodynamic activity. Chem Mater 29:1856–1863. https://doi.org/10.1021/acs.chemmater.7b00207
Zhang Y, Dang M, Tian Y, Zhu Y, Liu W, Tian W et al (2017b) Tumor acidic microenvironment targeted drug delivery based on pHLIP-modified mesoporous organosilica nanoparticles. ACS Appl Mater Interfaces 9:30543–30552. https://doi.org/10.1021/acsami.7b10840
Zhang H, Zhu Y, Shen Y (2018) Microfluidics for cancer nanomedicine: from fabrication to evaluation. Small 14:e1800360. https://doi.org/10.1002/smll.201800360
Zhao N, Pei SN, Qi J, Zeng Z, Iyer SP, Lin P et al (2015) Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia. Biomaterials 67:42–51. https://doi.org/10.1016/j.biomaterials.2015.07.025
Zhong S, Jeong JH, Chen Z, Chen Z, Luo JL (2020) Targeting tumor microenvironment by small molecule inhibitors. Transl Oncol 13:57–69. https://doi.org/10.1016/j.tranon.2019.10.001
Zhou Q, Hou Y, Zhang L, Wang J, Qiao Y, Guo S et al (2017) Dual-pH sensitive charge-reversal nanocomplex for tumor-targeted drug delivery with enhanced anticancer activity. Theranostics 7:1806–1819. https://doi.org/10.7150/thno.18607
Zhu JY, Zeng X, Qin SY, Wan SS, Jia HZ, Zhuo RX et al (2016) Acidity-responsive gene delivery for “superfast” nuclear translocation and transfection with high efficiency. Biomaterials 83:79–92. https://doi.org/10.1016/j.biomaterials.2016.01.003
Zou Y, Fang Y, Meng H, Meng F, Deng C, Zhang J et al (2016) Self-crosslinkable and intracellularly decrosslinkable biodegradable micellar nanoparticles: a robust, simple and multifunctional nanoplatform for high-efficiency targeted cancer chemotherapy. J Controlled Release 244:326–335. https://doi.org/10.1016/j.jconrel.2016.05.060
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Juthi, A.Z., Aquib, M., Farooq, M.A. et al. Theranostic applications of smart nanomedicines for tumor-targeted chemotherapy: a review. Environ Chem Lett 18, 1509–1527 (2020). https://doi.org/10.1007/s10311-020-01031-8
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DOI: https://doi.org/10.1007/s10311-020-01031-8