Self-delivery oxidative stress amplifier for chemotherapy sensitized immunotherapy

Zhao, Lin‐Ping; Zheng, Rongrong; Liu, Lingshan; Chen, Xiayun; Guan, Runtian; Ni, Yang; Chen, A‐Li; Yu, Xiyong; Cheng, Hong; Li, Shiying

doi:10.1016/j.biomaterials.2021.120970

Cited by 56 publications

(38 citation statements)

References 50 publications

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“…As one of the best characterized classical chemotherapeutic agents, doxorubicin (DOX) has been widely utilized in the clinical practice for cancer treatment. Moreover, DOX-induced immunogenic chemotherapy can initiate immunogenic cell death (ICD), which is considered as a distinctive cell death program that can elicit an immune response by exposing death-associated molecular patterns (DAMPs) on the surface of dying cancer cells to induce antitumor immune effects 9 - 11 . Unfortunately, chemotherapy alone cannot to provoke profound ICD to a satisfactory extent, largely due to the immunosuppressive tumor microenvironment 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, DOX-induced immunogenic chemotherapy can initiate immunogenic cell death (ICD), which is considered as a distinctive cell death program that can elicit an immune response by exposing death-associated molecular patterns (DAMPs) on the surface of dying cancer cells to induce antitumor immune effects 9 - 11 . Unfortunately, chemotherapy alone cannot to provoke profound ICD to a satisfactory extent, largely due to the immunosuppressive tumor microenvironment 11 . Worse still, because efflux proteins, especially P-glycoprotein (P-gp), are overexpressed on the plasma membranes of drug-resistant breast cancer cells, DOX that reaches the cytoplasm is rapidly pumped out of the cell, thereby reducing the cellular drug concentration 12 - 14 .…”

Section: Introductionmentioning

confidence: 99%

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Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy

Jiang¹,

Chen²,

Guo³

et al. 2022

Theranostics

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Rationale: Multidrug resistance (MDR) and metastasis of breast cancer remain major hurdles in clinical anticancer therapy. The unsatisfactory outcome is largely due to insufficient cytotoxicity of chemotherapeutic agents and limited immunogenic cell death (ICD). On the other hand, efflux proteins, especially P-glycoprotein (P-gp), can recognize and promote the efflux of drugs from tumor cells. Methods: In this study, silver nanoparticles (Ag NPs) and peptide- functionalized doxorubicin ( P DOX) were used to prepare a theranostic nanocomposite (Ag-TF@ P DOX), which induced organelle-mediated immunochemotherapy and drug efflux protein inhibition in drug-resistant breast cancer cells (MCF-7/ADR) via a strategy based on endoplasmic reticulum (ER) stress and cell-nucleus penetration. Results: The silver nanoparticle-triggered persistent activation of ER stress synergizes with chemotherapy to enhance cytotoxicity and stimulate the ICD effect. It has the potential to enhance chemosensitivity by downregulating of P-gp expression due to the increased production of ATP-consuming chaperones. In addition, the novel peptide (CB5005), which not only penetrates the cell membrane but also has a nuclear localization sequence, is conjugated to DOX to improve both cellular internalization and intranuclear accumulation. Moreover, surface TA-Fe 3+ engineering endows the nanocomposite with ATP-responsive disassembly and ATP depletion properties to improve biocompatibility and decrease ATP-dependent drug efflux. Ag-TF@ P DOX has potential as a dual-mode (PAI/MRI) contrast-enhanced agent for realizing theranostic guidance. Conclusion: This theranostic nanocomposite greatly restricts the growth of drug-resistant breast tumors and activates a strong immune response as well, providing an opportunity for the development of therapeutics that reverse tumor MDR and metastasis at the subcellular level.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy

Jiang¹,

Chen²,

Guo³

et al. 2022

Theranostics

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“…Among the broad spectrum of chemotherapeutic drugs, doxorubicin (Dox) has been proven capable of inducing ICD, thereby eliciting certain levels of antitumor immune responses accompanying chemotherapy [ 59 – 61 ]. By virtue of the π-π stacking and coordination effect among Cu 2+ , DOX and NLG919, Zhao et al designed and prepared a self-assembled nanosized oxidative stress amplifier (designated as Cu-DON) to achieve chemotherapy sensitized immunotherapy [ 62 ]. Following accumulation of Cu-DON NPs at tumor tissue via classical EPR effects, their GSH-responsive drug release behavior will initiate DOX-based immunogenic chemotherapy to inhibit primary tumor.…”

Section: Nanomedicine-instructed Chemotherapy Synergistic Cancer Therapymentioning

confidence: 99%

Nanomedicine-enabled chemotherapy-based synergetic cancer treatments

Shi

2022

J Nanobiotechnol

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Chemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible. Graphical Abstract

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“…[19][20][21] In particular, uniform nanosized nanomedicines with high drug loading capability could be obtained to improve the physicochemical properties, pharmacokinetics and pharmacodynamics of drugs. 22,23 Nevertheless, it was difficult to construct an ideal SDN with different antitumor drugs possessing great assembly potential and collaborative mechanisms. Moreover, such an SDN with GSH-depleting ability had been rarely reported but is urgently needed for enhanced photodynamic tumor therapy by disrupting the redox homeostasis.…”

Section: Introductionmentioning

confidence: 99%

A carrier free photodynamic oxidizer for enhanced tumor therapy by redox homeostasis disruption

Zheng

Chen

et al. 2022

Biomater. Sci.

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Self-delivery oxidative stress amplifier for chemotherapy sensitized immunotherapy

Cited by 56 publications

References 50 publications

Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy

Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy

Nanomedicine-enabled chemotherapy-based synergetic cancer treatments

A carrier free photodynamic oxidizer for enhanced tumor therapy by redox homeostasis disruption

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