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Dual drug-paired polyprodrug nanotheranostics reverse multidrug resistant cancers via mild photothermal-cocktail chemotherapy

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Abstract

Combating multidrug resistance (MDR) of tumors is still challenging for clinical chemotherapy, cocktail chemotherapy (CCT), and currently widely-studied nanodrug-based treatments. Inspired by different MDR-overcoming and antitumor mechanisms of CCT and photothermal therapy (PT), a dual drug-paired polyprodrug nanoparticle (PDCN25-CDDP) was constructed to achieve the combination therapy PT–CCT for reversing MDR and combating multidrug resistant cancers. The PT–CCT treatment can greatly downregulate the P-gp expression level and achieve utmost MDR-reversal and antitumor efficacy by both a cocktail effect of CCT and a synergistic effect of CCT with PT; meanwhile, PT can inhibit the expression of heat shock protein 90 and enhance the thermosensitivity of cancer cells. Upon NIR irradiation, PDCN25-CDDP in vivo produced a selective tumor accumulation effect and relatively deep tumor penetration, as evidenced by fluorescent and photoacoustic imaging and CLSM. The mild PT–CCT treatment completely eradicated MCF-7/ADR and OVCAR-3/DDP tumors without skin damage or tumor recurrence for 30 days, exhibiting synergistic MDR-reversal and superior antitumor efficacy in vivo. Importantly, this work provides an innovative strategy for reversing MDR and combating DOX-resistant breast and CDDP-resistant ovarian cancers.

Graphical abstract: Dual drug-paired polyprodrug nanotheranostics reverse multidrug resistant cancers via mild photothermal-cocktail chemotherapy

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Publication details

The article was received on 05 Jul 2019, accepted on 29 Jul 2019 and first published on 29 Jul 2019


Article type: Paper
DOI: 10.1039/C9TB01368G
J. Mater. Chem. B, 2019, Advance Article

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    Dual drug-paired polyprodrug nanotheranostics reverse multidrug resistant cancers via mild photothermal-cocktail chemotherapy

    C. Du, Y. Ding, J. Qian, R. Zhang and C. Dong, J. Mater. Chem. B, 2019, Advance Article , DOI: 10.1039/C9TB01368G

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