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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. [ABSTRACT FROM AUTHOR]

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d -α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart "switch" and tumor-targeted "guider", had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency. Image 1 [ABSTRACT FROM AUTHOR]