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Positively charged helical chain-modified stimuli-responsive nanoassembly capable of targeted drug delivery and photoacoustic imaging-guided chemo-photothermal synergistic therapy

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Abstract

In cancer treatment, surface modification by penetrating peptides and size control have been exploited as the two main strategies to tackle the problems of deep tumor penetration and cell internalization for nanocarriers. Polymeric nanocarriers with small size are beneficial for deep tumor penetration; however, they always undergo rapid clearance during body circulation and have low tumor accumulation efficiency. To solve this dilemma, a tumor-targeted size-switchable CPT/IR780@H30-PCL-PPI(L−)/PEI(–COOH/FA) nanoassembly with a “pomegranate” construction was designed in this study. Initially, it possessed a large size and negative charge to meet the long blood circulation time but rapidly disassembled into small-sized guanidinium and helical chain-modified unimolecular micelle-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 cell internalization due to the guanidinium group-modified helical chains, which exhibited a similar structure to that of the cell penetrating peptides. In addition, the nanoassembly exhibited strong photothermal conversion and acoustic generation efficiency. Moreover, the generated heat significantly improved the drug release, thus realizing functional cooperativity and adaptability. This proof of concept can be supposed to be a significant progress in the design and preparation of tumor microenvironment-responsive drug delivery systems and their use for photoacoustic imaging-assisted chemo-photothermal synergistic therapy.

Graphical abstract: Positively charged helical chain-modified stimuli-responsive nanoassembly capable of targeted drug delivery and photoacoustic imaging-guided chemo-photothermal synergistic therapy

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Publication details

The article was received on 12 Jan 2019, accepted on 15 Feb 2019 and first published on 08 Mar 2019


Article type: Paper
DOI: 10.1039/C9BM00055K
Citation: Biomater. Sci., 2019, Advance Article

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    Positively charged helical chain-modified stimuli-responsive nanoassembly capable of targeted drug delivery and photoacoustic imaging-guided chemo-photothermal synergistic therapy

    J. Zhang, Z. Qiao, H. Liu, J. Song and J. Yin, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM00055K

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