Recent advances in lipid-engineered multifunctional nanophytomedicines for cancer targeting

Highlights

• Phytoconstituents are new emerging therapeutics against cancer.

• These molecules can be combined with existing therapeutics for better outcome.

• Lipidic vesicles are compatible carriers and mimic the biological membrane.

• Nanoengineering in lipidic carriers enhances its efficacy.

Abstract

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current treatments available for variety of cancers is considered to be suboptimal due to the pathophysiological challenges associated with the disease which limits the efficacy of the anticancer drugs. Moreover, the vulnerability towards off-target effects and high toxicity also limits the use of drugs for the treatment of cancers. Besides, the biopharmaceutical challenges like poor water solubility and permeability of the drugs, along with the absence of active targeting capability further decreases the utility of drugs in cancer therapy. As a result of these deficiencies, the current therapeutic strategies face noncompliance to patients for providing meaningful benefits after administration. With the advancements in nanotechnology, there has been a paradigm shift in the modalities for cancer treatment with the help of phytomedicine-based nanosized drug delivery systems coupled with variegated surface-engineering strategies for targeted drug delivery. Among these delivery systems, lipid-based nanoparticles are considered as one of the highly biocompatible, efficient and effective systems extensively explored for anticancer drug delivery. These include diverse range of systems including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers and supramolecular carriers, which alters pharmacokinetic and biodistribution of the drugs for active targeting to the desired site of action by overcoming the biopharmaceutical challenges associated with anticancer drug delivery. The present review endeavours to provide a comprehensive account on the recent advances in the application of lipid-based nanostructured systems for improving the pharmacotherapeutic performance of phytomedicines for cancer targeting application.

Introduction

Hippocrates explain cancer as finger like projections which mind the crab shape [1,2]. Cancer is characterized by abnormal growth of cell with potential to invade other areas or distant part of body [[3], [4], [5]]. Different terms are used for explaining the cancers and malignant cells, with all depend on its origin whether it is sarcoma (like fat, bones, muscles, cartilages, and blood vessels), carcinoma (like skin or any internal tissue), leukemia (like bone marrow) or lymphoma (like immune system). As per WHO cancer report of 2018, it is second leading cause of death globally, which accounts for 9.6 million deaths [6,7]. Cancer cells have six prominent features: (i) self-sufficient signals; (ii) no sensitivity to anti-growth signals; (iii) apoptosis invasion; (iv) limited repetition in potential; (v) sustaining of angiogenesis; (vi) metastasis of tissue and its invasion [8]. Most common cancer includes lung, colorectal, prostate, liver, stomach and head-neck carcinomas. Symptoms and signs of cancer specifically depend on its size, type, location, extent to the tissues and organs. There are more than 100 types of cancers which exist till date. In humans, general signs and symptoms due to presence of cancer cells are incomprehensible events of pain, night sweats, fever, weight loss, unusual bowel movements, prominent events of cough, lumps [9,10].

Almost 30% of deaths arising due to cancer can be thwarted by slight modification or avoidance of risk factors. Various approaches employed for cancer treatment are hormone-based therapy, surgical interventions, chemotherapy, photodynamic therapy, immunotherapy, radiation therapy and genetic therapy [[11], [12], [13]]. Treatment choice depends on the stage and type of tumour and organ affected. For example, in case of non metastatic cancer, major goal is to eradicate tumour from regional lymph nodes and prevention of metastasis stage. Eradication of cancer can be achieved by surgical removal of cancer site and near by lymph nodes along with systemic administration of anti cancer moieties (preoperative or postoperative). In case of metastatic cancer, major goal is prolongation of life and decrease of morbidity. Presently, metastatic cancer remains incurable and systemic therapy is done to prolong the prognosis of disease. As per the WHO guidelines in which new treatment options were adopted with an initiative for cancer treatment especially in low- and middle-income nations [14,15]. Treatment of cancer is highly herculean task due to various unwanted events like aggression in proliferation of tumour and its spreading to multiple organs, therapeutic resistance, heterogenous in metastasis, barriers in drug permeation. Most common approach practiced in case of cancer therapy is chemotherapy but it imparts acute as well as chronic side effects to patients and thus overall hinders the quality of life [16]. Recent cancer treatment patterns have been changed with targeting to oncogenes and immune oncology-based cancerous ailments [17]. However, still there are miles of way existing for overcoming the challenges pertaining to cancer therapy. Sequence-based analysis for pre-screening of molecules in clinical research is advantageous but it restricts the clinical application owing to large volume of genomic data [18]. Also, precision-based oncology treatment is limited due to the heterogeneity as well as resistance acquired by cancer cells, while immune check-point inhibitors does not aid in success to cancer treatment due to lack of suitable validation process for markers.