Preparation Of Tumor Microenvironment-Responsive Nanoassemblies Based On H30 Micelles And Photoacoustic Imaging-Mediated Photothermal/Chemical Synergistic Therapy

In cancer treatment,size control and penetrating peptide modification have been exploited as two main strategies to tackle the problems of deep tumor penetration and cell internalization for nanocarriers.Polymeric nanocarriers with ultrasmall size are favorable for tumor penetration,while,they are always subjected to rapid clearance in systemic circulation and have low tumor accumulation efficiency.To solve this dilemma,tumor targeted size-switchable CPT/IR780@H30-PCL-PPI(L-)/PEI(-COOH/FA)nanoassembly with a “cluster-bomb” construction was designed in this contribution,which possess large negatively charged initial size to meet the long blood circulation,but rapidly disassemble into small-sized guanidinium and helical chains modified unimolecular micelles based nanocarriers,CPT/IR780@H30-PCL-PPI(L-/+),at tumor sites due to the tumor microenvironment induced charge reversal.The CPT/IR780@H30-PCL-PPI(L-/+)assembly could efficiently expand the penetration depth and accelerate the cell internalization benefiting from the guanidinium groups modified helical chains,which has a similar structure to cell penetrating peptide.Not only that,the nanoassembly exhibited strong photothermal conversion and acoustic generation efficiency.Moreover,the generated heat significantly improved the drug release,realizing functional cooperativity and adaptability.This proof-of-concept can be considered as a significant step in the development of tumor specific stimuli-responsive drug delivery systems and utilized for photoacoustic imaging guided synergistic chemo-photothermal therapy.