Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy

Xu, Fang; Zhu, Jianzhi; Lin, Lizhou; Zhang, Changchang; Sun, Wenjie; Fan, Yu; Yin, Fang‐Fang; Hest, Jan C. M. van; Wang, Han; Du, Lianfang; Shi, Xiangyang

doi:10.7150/thno.43402

Cited by 58 publications

(52 citation statements)

References 31 publications

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“… 212 Disulfide moieties are able to be included in many types of polymer nanoparticles. 213 − 215 For example, Zhong et al . synthesized polymer vesicles from poly(ethylene glycol)- block -poly(trimethylene carbonate- co -dithiolane trimethylene carbonate)- block -poly(ethylenimine).…”

Section: Redox (Glutathione/ros)mentioning

confidence: 99%

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

2021

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Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic tools. The design of materials that undergo morphological or chemical changes in response to specific biological cues or pathologies will be an important area of research for improving efficacies of existing therapies and imaging agents, while also being promising for developing personalized theranostic systems. Internal stimuli-responsive systems can be engineered across length scales from nanometers to macroscopic and can respond to endogenous signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, and nucleic acids by incorporating synthetic bio-inspired moieties or natural building blocks. This Review will summarize response mechanisms and fabrication strategies used in internal stimuli-responsive materials with a focus on drug delivery and imaging for a broad range of pathologies, including cancer, diabetes, vascular disorders, inflammation, and microbial infections. We will also discuss observed challenges, future research directions, and clinical translation aspects of these responsive materials.

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Section: Redox (Glutathione/ros)mentioning

confidence: 99%

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

2021

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“…All the time we explored various NGs that having the controllable size, deformable softness, highly porous network, excellent biocompatibility and stimuli-responsiveness can be employed as functional nanocarriers for improved tumor theranostics [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ]. In particular, the biocompatible PVCL-based NGs exist a volume phase transition temperature (VPTT) of about 35 °C which is close to body temperature, and high cargo loading capacity along with enhanced tumor accumulation for biomedical purposes [ [26] , [27] , [28] ]. Despite all that, these NGs also display low tissue penetration, insufficient cellular internalization and high liver retention, which seriously limit their further clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

Ouyang

et al. 2021

Bioactive Materials

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Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy. Here, the PAMAM dendrimer decorated PVCL-GMA nanogels (NGs) were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma. By an ingenious design, the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization. After G2 dendrimer decoration, the overall charge is changed from neutral to positive, and the NGs-G2 display the whole charge nature of positively charged corona and neutral core. Importantly, the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo . As a consequence of this alteration, the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation, enhanced tumor uptake, and promoted drug release, resulting in the significantly augmented antitumor efficacy with low side effects. Remarkably, this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake. Moreover, the NGs-G2 also displayed thermal/pH dual-responsive behaviors, excellent biocompatibility, improved cellular uptake, and stimuli-responsive drug release. Encouragingly, this work demonstrates a novel insight into the strategy for optimizing design, improving biodistribution and enhancing theranostic efficacy of nanocarriers.

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“… 10 , 39 − 41 Manganese dioxide (MnO 2 ) can exert a redox reaction with GSH to yield glutathione disulfide and Mn 2+ , thus effectively down-regulating the GSH level, and interestingly, the consequently generated Mn 2+ can be further used as T 1 -weighted magnetic resonance (MR) imaging contrast agents for tumor imaging and detection. 10 , 42 − 47 Therefore, the integration of CAT and MnO 2 in the PDT process holds great potential to promote PDT performance by simultaneously reoxygenating the hypoxic tumor tissue, depleting the intracellular GSH, and providing MR imaging guidance.…”

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confidence: 99%

Surface-Charge-Switchable Nanoclusters for Magnetic Resonance Imaging-Guided and Glutathione Depletion-Enhanced Photodynamic Therapy

et al. 2020

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Photodynamic therapy (PDT) is an effective noninvasive therapeutic method that employs photosensitizers (PSs) converting oxygen to highly cytotoxic singlet oxygen ( 1 O 2 ) under light irradiation. The conventional PDT efficacy is, however, compromised by the nonspecific delivery of PSs to tumor tissue, the hypoxic tumor microenvironment, and the reduction of generated 1 O 2 by the intracellular antioxidant glutathione (GSH). Herein, an intelligent multifunctional synergistic nanoplatform (CMGCC) for T 1 -weighted magnetic resonance (MR) imaging-guided enhanced PDT is presented, which consists of nanoparticles composed of catalase (CAT) and manganese dioxide (MnO 2 ) that are integrated within chlorin-e6-modified glycol chitosan (GC) polymeric micelles. In this system, (1) GC polymers with pH-sensitive surface charge switchability from neutral to positive could improve the PS accumulation within the tumor region, (2) CAT could effectively reoxygenate the hypoxic tumor via catalyzing endogenous hydrogen peroxide to O 2 , and (3) MnO 2 could consume the intracellular GSH while simultaneously producing Mn 2+ as a contrast agent for T 1 -weighted MR imaging. The CMGCC particles possess uniform size distribution, well-defined structure, favorable enzyme activity, and superior 1 O 2 generation ability. Both in vitro and in vivo experiments demonstrate that the CMGCC exhibit significantly enhanced PDT efficacy toward HeLa cells and subcutaneous HeLa tumors. Our study thereby demonstrates this to be a promising synergistic theranostic nanoplatform with highly efficient PDT performance for cancer therapy.

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Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy

Cited by 58 publications

References 31 publications

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

Surface-Charge-Switchable Nanoclusters for Magnetic Resonance Imaging-Guided and Glutathione Depletion-Enhanced Photodynamic Therapy

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