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Achieving Traceless Ablation of Solid Tumor without Recurrence by Mild Photothermal-Chemotherapy of Dual Stimuli-Responsive Polymer-Drug Conjugate Nanoparticle

Abstract

Although photothermal therapy (PT) and photothermal-chemotherapy (PT-CT) treatments have achieved complete ablation of solid tumor, they are often implemented at > 50 oC under high intensity and high dose of NIR irradiation, concomitantly inducing heavy skin burning, tissue damage, and ugly scarring. Moreover, the residual tumor cells in treated site can not be completely eradicated, resulting in tumor recurrence and metathesis. These key obstacles prohibited PT and PT-CT treatments from clinical transition, thus achieving traceless ablation of solid tumor without recurrence is still challenging for real applications. To leverage the hyperthermia and the high drug-loading capacity in polyprodrug for achieving mild PT-CT, we rationally design a novel kind of intracellular pH and reduction-cleavable chlorambucil prodrug and synthesize the high drug-loading polydopamine-chlorambucil conjugate nanoparticles (PDCBs). The PDCBs show good photothermal properties, intracellular pH and reduction-cleavable, and external NIR-triggered drug release profiles. The PDCB40 (40 wt% CB) + mild NIR irradiation could facilitate cellular internalization and subcellular trafficking, generating an excellent and synergistic antitumor effect in vitro. Pharmacokinetics and small animal fluorescent and photoacoustic imagings demonstrate that PDCB40 had 3.6-fold longer blood circulation time than free CB and attained selective tumor accumulation, simultaneously inducing 4.1-fold stronger photoacoustic signal than control. By using one intravenous injection of PDCB40 and single mild NIR irradiation, this simple and mild PT-CT treatment achieved non-discerned tumor on 6th day, and traceless and complete ablation of solid MCF-7 tumor without recurrence in 50 days, opening up a new avenue for precise cancer therapy with real application potential.

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Publication details

The article was received on 14 Sep 2018, accepted on 05 Dec 2018 and first published on 07 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB02432D
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Achieving Traceless Ablation of Solid Tumor without Recurrence by Mild Photothermal-Chemotherapy of Dual Stimuli-Responsive Polymer-Drug Conjugate Nanoparticle

    C. Du, Y. Ding, J. Qian, R. Zhang and C. Dong, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB02432D

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