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Acidity-responsive shell-sheddable camptothecin-based nanofibers for carrier-free cancer drug delivery

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Abstract

Small molecular prodrugs that self-assemble into nanoparticles have many advantages over commonly studied nanomedicines based upon nanoscale carriers such as liposomes, micelles and polymeric nanoparticles. These carrier-free nanodrugs exhibit favorable nanoproperties without the help of a nanocarrier, and they have many unique merits, such as a simple synthetic procedure, well-defined structure and high drug loading capacity. To date, most of these carrier-free nanodrugs have been spherical and very few nonspherical nanodrugs have been synthesized and studied. Herein, we report a camptothecin (CPT) prodrug that self-assembles into nanofibers. These carrier-free CPT nanofibers have a width of approximately one hundred nanometers and a length of several micrometers. The cellular uptake and tumor penetration behaviour of these nanofibers were observed by time-lapse video microscopy. These nanofibers can rapidly enter cancer cells by penetrating the cell membrane, gradually dissolve intracellularly and efficiently release the active drug. Coating the surface of these nanofibers with a pH-responsive PEG layer improves the stability of these nanofibers and shields their positive charge to minimize nonspecific interactions. These pH-responsive nanofibers are sheddable in the acidic tumor microenvironment and deliver carried cargoes deep into tumors. Our findings demonstrate that small molecular CPT prodrugs that form nanofibers are efficient for cancer drug delivery.

Graphical abstract: Acidity-responsive shell-sheddable camptothecin-based nanofibers for carrier-free cancer drug delivery

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Publication details

The article was received on 07 May 2019, accepted on 22 Jul 2019 and first published on 25 Jul 2019


Article type: Paper
DOI: 10.1039/C9NR03872H
Nanoscale, 2019, Advance Article

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    Acidity-responsive shell-sheddable camptothecin-based nanofibers for carrier-free cancer drug delivery

    Z. Zhou, Y. Piao, L. Hao, G. Wang, Z. Zhou and Y. Shen, Nanoscale, 2019, Advance Article , DOI: 10.1039/C9NR03872H

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