Photodynamic therapy (PDT) is an effective and noninvasive therapeutic strategy employing light-triggered singlet oxygen (SO) and reactive oxygen species (ROS) to kill lesional cells. However, for effective in vivo delivery of PDT agent into the cancer cells, various biological obstacles including blood circulation and condense extracellular matrix (ECM) in the tumor microenvironment (TME) need to be overcome. Furthermore, the enormous challenge in design of smart drug delivery systems is meeting the difference, even contradictory required functions, in different steps of the complicated delivery process. To this end, we present that TME-activatable circular pyrochlorophyll A (PA)-aptamer-PEG (PA-Apt–CHO–PEG) nanostructures, which combine the advantages of PEG and aptamer, would be able to realize efficient in vivo imaging and PDT. Upon intravenous (i.v.) injection, PA-Apt–CHO–PEG shows “stealth-like” long circulation in blood compartments without specific recognition capacity, but once inside solid tumor, PA-Apt–CHO–PEG nanostructures are cleaved and then form PA-Apt Aptamer-drug conjugations (ApDCs) in situ, allowing deep penetration into the solid tumor and specific recognition of cancer cells, both merits, considering anticipated future clinical translation of ApDCs.

光动力疗法（PDT）是一种有效的非侵入性治疗策略，采用光触发单线态氧（SO）和活性氧（ROS）杀死病灶细胞。然而，为了将PDT剂有效地体内递送到癌细胞中，需要克服各种生物学障碍，包括血液循环和肿瘤微环境（TME）中的凝聚细胞外基质（ECM）。此外，智能药物输送系统设计中的巨大挑战在于在复杂的输送过程的不同步骤中满足差异，甚至是相互矛盾的所需功能。为此，我们提出结合了PEG和适体优势的TME活化环状叶绿素A（PA）-适体-PEG（PA-Apt-CHO-PEG）纳米结构将能够实现高效体内成像和PDT。静脉内（iv）注射后，PA-Apt-CHO-PEG在血液腔室中显示出“隐身”长循环，没有特定的识别能力，但是一旦进入实体瘤，PA-Apt-CHO-PEG纳米结构被裂解，然后形成PA -Apt适体药物缀合（ApDCs）在原位，从而深深渗透到实体瘤和特异性识别肿瘤细胞，二者的优点，考虑到未来预期ApDCs的临床转化。