Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer

Wen, Ming‐Shien; Chen, Qiling; Xu, Weiguo; Yu, Meng; Yang, Yuanyuan; Zou, Binhua; Zhang, Yu Shrike; Ding, Jianxun; Yu, Zhiqiang

doi:10.1007/s12274-020-3124-y

Cited by 127 publications

(76 citation statements)

References 49 publications

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“…Interestingly, HA and cisplatin could also be co-assembled with a second drug to form multidrug NG (Figure 1C), thus easily realizing the combination therapy especially for cancer . The cationic-aromatic drugs (CA drugs) containing aromatic ring and positive charges, such as chemotherapeutics (Zhang et al, , 2018Yu et al, 2020;Ma et al, 2021), kinase inhibitors , and photosensitizers/dyes (Zhang and Tung, 2018a), could be easily self-assembled into the HA/Cis NG. The positive charges of CA drugs are believed to interact with HA through electrostatic interaction while the aromatic ring contributes to the hydrophobic interaction and π-π stacking of drugs, which collectively facilitates the encapsulation of CA drug into the NG.…”

Section: Self-assembled Hyaluronan (Ha) Ngmentioning

confidence: 99%

“…have been successfully co-assembled into the HA/Cis NG (Gao et al, 2021). The HA/Cis NG with doxorubicin encapsulation demonstrated a pH-and GSH-responsive release behavior, which was able to help combat the cancer drug resistance (Zhang and Tung, 2018b;Ma et al, 2021). Generally, the HA/Cis NG could efficiently realize a CD44-targeted delivery for cancers such as cisplatin monotherapy and cisplatin-based combination therapy.…”

Section: Self-assembled Hyaluronan (Ha) Ngmentioning

confidence: 99%

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Self-Assembled Nanogels Based on Ionic Gelation of Natural Polysaccharides for Drug Delivery

Wang

Deng

Gao

et al. 2021

Front. Bioeng. Biotechnol.

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The polysaccharides (PS) have been widely used as biomaterials in drug delivery, due to their excellent biocompatibility, ease of functionalization, and intrinsic biological activities. Among the various PS-based biomaterials, the self-assembled PS nanogels (NG) featuring facile preparation are attracting evergrowing interests in various biomedical applications. Specifically, NG derived from the self-assembly of natural PS well maintain both the physicochemical and biological properties of PS while avoiding the chemical modification or alteration of PS structure, representing a potent drug delivery system for various therapeutic agents. In this review, the natural PS, such as chitosan, alginate, and hyaluronan, for self-assembled NG construction and their advantages in the applications of drug delivery have been summarized. The residues, such as amine, carboxyl, and hydroxyl groups, on these PS provide multiple sites for both ionic cross-linking and metal coordination, which greatly contribute to the formation of self-assembled NG as well as the drug loading, thus enabling a wide biomedical application of PS NG, especially for drug delivery. Future developments and considerations in the clinical translation of these self-assembled PS NG have also been discussed.

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Section: Self-assembled Hyaluronan (Ha) Ngmentioning

confidence: 99%

Section: Self-assembled Hyaluronan (Ha) Ngmentioning

confidence: 99%

Self-Assembled Nanogels Based on Ionic Gelation of Natural Polysaccharides for Drug Delivery

Wang

Deng

Gao

et al. 2021

Front. Bioeng. Biotechnol.

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“…To address this, we constructed an orthotopic rectal cancer model, and proved that BMS202 would boost tumor responses to treatment of REG. To reduce anticancer drug-associated sideeffects and improve treatment efficacy, various polymer-based carriers have been designed by researchers and employed in drug delivery (Ding et al, 2019a;Ding et al, 2019b;Sun et al, 2019;Zheng et al, 2020;Ma et al, 2021). In addition to the popular nanoparticle-based drug carriers (Wang et al, 2018;Chen et al, 2020;Feng et al, 2020;Jiang et al, 2020;Zhang et al, 2020), hydrogels were also designed and optimized in drug delivery nowadays (Guo et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Molecular Targeted Agent and Immune Checkpoint Inhibitor Co-Loaded Thermosensitive Hydrogel for Synergistic Therapy of Rectal Cancer

Zhang

Liu

et al. 2021

Front. Pharmacol.

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Molecular targeted therapy has been proved effective in treatment of rectal cancer. Up-regulated expression of programmed death ligand-1 (PD-L1) was observed after the management of molecular targeted therapy, which made the therapeutic effect discounted. Tumors with higher PD-L1 expression were more sensitive and responsive to treatment of PD-L1 inhibitor. Therefore, the combination of molecular targeted therapy and immune checkpoint blockade makes sense. In this study, the copolymers of poly (ethylene glycol)-block-poly (L-leucine) (PEG-PLLeu) were synthesized as a thermosensitive hydrogel composite for consecutive release of regorafenib (REG) and BMS202. The mechanical properties of PEG-PLLeu were investigated, confirming that PEG-PLLeu (5 wt.%) was suitable for in situ injection as drug-delivery composite at low temperature and stable after sol-gel transition at body temperature. Importantly, the double drug loaded hydrogel showed superior antitumour activity over single drugs in an orthotopic rectal cancer model (CT26-Luc). Further analysis of the tumor tissues suggested that REG upregulated the expression of PD-L1 in tumor tissues. In addition, the immunosuppressive tumor microenvironment of CT26-Luc tumor was distinctly relieved under the effect of BMS202, as characterized by increased infiltration of CD8+ T cells in tumors and enhanced secretion of antitumour cytokines (IFN-γ and TNF-α). Moreover, the drug-loaded composite showed no obvious toxicity in histological analysis. Taken together, the administration of REG and BMS202 in the PEG-PLLeu composite could induce a synergistic effect in in situ treatment of rectal cancer without obvious toxicity, and thus represented a potential strategy for enhanced in situ therapeutic modality.

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“…Most chemotherapy drugs currently have no targeting capabilities, and act on both diseased and non-diseased sites, leading to low therapeutic indices and severe side effects (Padmanabhan et al, 2016 ; Picheth et al, 2017 ; Guo et al, 2018 ; Paris et al, 2019 ; Wang et al, 2019 ). A targeted drug delivery system can increase chemotherapy drug accumulation specifically at target sites, while reducing non-target impacts (Ding et al, 2019 ; Li et al, 2020 ; Zheng et al, 2020 ; Feng et al, 2021 ; Chen et al, 2021 ; Wang et al, 2021 ; Ma et al, 2021 ). Moreover, targeted microbubbles are both chemically stable and biodegradable, and exhibit prolonged circulation in the blood, with localized drug release (Lux et al, 2017 ; Chen et al, 2019 a,b; Szablowski et al, 2019 ; Brambila et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Synergic fabrication of pembrolizumab loaded doxorubicin incorporating microbubbles delivery for ultrasound contrast agents mediated anti-proliferation and apoptosis

Liu

Chen

et al. 2021

Drug Delivery

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This study evaluated pembrolizumab-conjugated, doxorubicin (DOX)-loaded microbubbles (PDMs) in combination with ultrasound (US) as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Pembrolizumab, a monoclonal CD20 antibody, was attached to the surfaces of DOX-loaded microbubbles. PDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of PDMs in combination with ultrasound (PDMs þ US) were evaluated in vitro in CD20þ and CD20-cell lines, and its antitumor activities were assessed in Raji (CD20þ) and Jurkat (CD20-) lymphoma cell-grafted mice. PDMs specifically bound to CD20þ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via US. PDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (p < 0.05). PDMs þ US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments (p < .05). Our results showed that PDMs þ US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20þ B cell lymphoma growth in vivo. Targeted PDMs could be employed as US molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with US for CD20þ B cell malignancy treatment.

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Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer

Cited by 127 publications

References 49 publications

Self-Assembled Nanogels Based on Ionic Gelation of Natural Polysaccharides for Drug Delivery

Self-Assembled Nanogels Based on Ionic Gelation of Natural Polysaccharides for Drug Delivery

Molecular Targeted Agent and Immune Checkpoint Inhibitor Co-Loaded Thermosensitive Hydrogel for Synergistic Therapy of Rectal Cancer

Synergic fabrication of pembrolizumab loaded doxorubicin incorporating microbubbles delivery for ultrasound contrast agents mediated anti-proliferation and apoptosis

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