Red Light Controlled PEG Deshielding From ROS-Sensitive Linkage-bridged Block Copolymer-based Nanocarriers For Enhancing The Therapeutic Effect Of Tumor

In order to solve the small molecule cancer drugs difficult problem such as solubility,side effects.It successfully increases the blood circulation time of the drug in the body and reduces the toxic side effect of the drug.However more and more studies have shown that polyethylene glycol also reduces the cellular uptake of drugs.Controlling poly?ethylene glycol??PEG?shielding/deshielding at the desired site of action exhibits great advantages for the organic combination of long circulation in blood and tumor site enhancement tumor cell uptake in vivo.Therefore,a variety of responsive "PEG deshielding" nano-drug carriers have been developed.However,the current PEG deshielding strategies were mainly designed by tumor acidity or specific high expression enzyme in tumor site;even so,these endogenous responses are also limited by tumor heterogeneity.We explored a photoinduced PEG deshielding nanocarrier TK-NP_Ce6&PTXe6&PTX to circumvent the aforementioned challenge.The TK-NP_Ce6&PTXencapsulating chlorin e6?Ce6?and paclitaxel?PTX?was self-assembled from an innovative thioketal?TK?linkage-bridged diblock copolymer of PEG with poly?d,l-lactic acid??PEG-TK-PLA?.We demonstrated that the high PEGylation of TK-NP_Ce6&PTXin blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time.At the desired site?tumor?,660-nm red light irradiation led to ROS generation in situ,which readily cleaved the TK linkage,resulting in PEG deshielding.Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers,achieving on-demand drug delivery and superior therapeutic efficacy.More importantly,this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery.