Abstract
The combination of chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) based on a single nanosystem is highly desirable for cancer treatment. In this study, we developed a versatile Pt(IV) prodrug-based nanodrug, PVPt@Cy NPs, to realize synchronous chemotherapy, PDT and PTT and integrate cancer treatment with bioimaging. To construct PVPt@Cy NPs, the amphiphilic Pt(IV)-based polymeric prodrug PVPt was synthesized by a facile one-pot coupling reaction, and then it was used to encapsulate an optotheranostic agent (HOCyOH, Cy) via hydrophobic interaction-induced self-assembly. These NPs would disaggregate under acidic, reductive conditions and NIR irradiation, which are accompanied by photothermal conversion and reactive oxygen species (ROS) generation. Moreover, the PVPt@Cy NPs exhibited an enhanced in vitro anticancer efficiency with 808-nm light irradiation. Furthermore, the PVPt@Cy NPs showed strong NIR fluorescence and photothermal imaging in H22 tumor-bearing mice, allowing the detection of the tumor site and monitoring of the drug biodistribution. Therefore, PVPt@Cy NPs displayed an enormous potential in combined chemo-phototherapy.
Highlights
Cancer is still one of the major health threats in the world
We develop a novel, multifunctional drug delivery system PVPt@Cy NPs based on the co-assembly of Pt(IV)-based polymeric prodrug (PVPt) and a modified cyanine dye 1-(2-hydroxyethyl)-2-((E)-2-((E)-3-((E)-2-(1-(2-hydroxyethyl)-3,3-dimethylindolin2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-ly)vinyl)-3,3-dimethyl-3H-indol-1-ium bromide (HOCyOH, denoted as Cy) for realizing combined chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) cancer treatment (Scheme 1)
In the 1H NMR spectrum (Figure S2), when the two peak signals at δ = 8.3 and 6.5 ppm were ascribed to the protons from the bridge between cyclopentane and cyclohexene, a peak at 1.6 ppm belonging to the methyl group appeared, and characteristic peaks of the benzene ring at 7.1–7.4 ppm were observed
Summary
Cancer is still one of the major health threats in the world. Chemotherapy, one of conventional treatment modalities, is a remarkable success in clinical practice [1]. The pHDL would rapidly collapse, resulting in compact structure disassembly and intracellular PTX burst drug release This system could facially realize fluorescence imaging-guided precision chemo-phototherapy. Previous studies confirmed that cyanine dyes and chemotherapeutic drugs co-loaded with nanoparticles showed application potency for chemo-phototherapy. Both cyanine dyes and chemotherapeutic drugs were usually incorporated in nanocarriers via electrostatic or hydrophobic interaction, resulting in a limited drug encapsulation capacity and unsatisfactory burst release of chemotherapeutic drugs. We develop a novel, multifunctional drug delivery system PVPt@Cy NPs based on the co-assembly of Pt(IV)-based polymeric prodrug (PVPt) and a modified cyanine dye 1-(2-hydroxyethyl)-2-((E)-2-((E)-3-((E)-2-(1-(2-hydroxyethyl)-3,3-dimethylindolin2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-ly)vinyl)-3,3-dimethyl-3H-indol-1-ium bromide (HOCyOH, denoted as Cy) for realizing combined chemotherapy, PTT and PDT cancer treatment (Scheme 1). AAddddii-ttiioonnaallllyy,, cciissppllaattiinn wwaass ooxxiiddiizzeedd ttoo DDHHPP [[3377,,3388]],, aanndd tthheenn wwee ssyynntthheessiizzeedd HHOO--PPtt--CCOOOOHH wwiitthh DDHHPPaannddSSAA[[3399]]..(P(PleleaasesererefefrertotoSSuupppporotrintigngInIfnofromrmataiotinonfofrotrhtehsepsepciefcicifiscynsythnetshiesrsoisutreo.u) te.)
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