A tumor acidity-driven transformable polymeric nanoassembly with deep tumor penetration and membrane-anchoring capability for targeted photodynamic therapy

Xu, Weilin; Wang, Junxia; Jin, Liangjie; Zhu, Yueqiang; Yang, Xianzhu

doi:10.1016/j.biomaterials.2021.121024

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…Once they arrive at the tumor site, their size decreases to achieve good tumor permeation and efficient cellular uptake. [104,105] Based on this strategy, Song and coworkers reported a two-stage size reduction process for deep tumor penetration and photoacoustic imagingguided tumor therapy. [106] As shown in Figure 5a, the pH and reduction responsive characteristics result in deep tumor penetration and localized drug release of their nanosystem (PEG-PCRVP/AuNR@PDOX) via a two-stage size decrease strategy.…”

Section: Size Decreasementioning

confidence: 99%

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Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy

Han

Foda

Zhao

2021

Adv Healthcare Materials

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Rapid development of nanotechnology provides promising strategies in biomedicine, especially in tumor therapy. In particular, the cellular uptake of nanosystems is not only a basic premise to realize various biomedical applications, but also a fatal factor for determining the final therapeutic effect. Thus, a systematic and comprehensive summary is necessary to overview the recent research progress on the improvement of nanosystem cellular uptake for cancer treatment. According to the process of nanosystems entering the body, they can be classified into three categories. The first segment is to enhance the accumulation and permeation of nanosystems to tumor cells through extracellular microenvironment stimulation. The second segment is to improve cellular internalization from extracellular to intracellular via active targeting. The third segment is to enhance the intracellular retention of therapeutics by subcellular localization. The major factors in the delivery can be utilized to develop multifunctional nanosystems for strengthening the tumor therapy. Ultimately, the key challenges and prospective in the emerging research frontier are thoroughly outlined. This review is expected to provide inspiring ideas, promising strategies and potential pathways for developing advanced anticancer nanosystems in clinical practice.

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Section: Size Decreasementioning

confidence: 99%

“…Charge Protonation [74][75][76]81] Charge shield [ 77,84] Size Size increase [ 90,91,93,94] Size decrease [101,102,105,106] Shape Morphologies [110][111][112][113] Sphere-to-rod [115,116,118] Surface modification…”

Section: Extracellular Microenvironmentmentioning

confidence: 99%

Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy

Han

Foda

Zhao

2021

Adv Healthcare Materials

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“…7,13,15,22 Poly(2-azepane ethyl methacrylate) (PAEMA) is an ultrahigh pH-sensitive polymer that can be protonated in the slightly acidic microenvironment of the tumor (pH 6.5-6.8) to adjust its charge and solubility, which endows it with wide applications in tumor-specific drug delivery. [23][24][25][26] Theoretically, protonated PAEMA simultaneously possesses cationic moieties (protonated tertiary amine) and hydrophobic moieties (hexamethylene). This implies that PAEMA may disrupt the plasma membranes of cancer cells at the tumor sites, while silencing cytotoxicity in blood circulation and normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Membrane-disruptive homo-polymethacrylate with both hydrophobicity and pH-sensitive protonation for selective cancer therapy

Geng

Wei

et al. 2023

J. Mater. Chem. B

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“…However, the strategies developed to date are usually enacted inside tumor cells, while the PDL1 specific binding aptamer (PDL1 aptamer) and CpG generally play their biological roles in the extracellular tumor microenvironment (TME). Besides, disruption of the tumor cell membrane has been proved to markedly increase the release of tumor antigens to enhance immunogenic cell death (ICD). ,− Therefore, we considered designing a membrane-targeted DNA nanomedicine that would anchor on a tumor cell membrane and finding a strategy to release internal PDL1 aptamer and CpG into the TME in response to specific stimulation.…”

Section: Introductionmentioning

confidence: 99%

Photocontrolled Spatiotemporal Delivery of DNA Immunomodulators for Enhancing Membrane-Targeted Tumor Photodynamic Immunotherapy

Wang

Liu

Duan

et al. 2022

ACS Appl. Mater. Interfaces

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Immunotherapy is emerging as a paradigm-shifting modality for treatment cancer. However, systemic administration of immunomodulators is usually accompanied by extra-tumor toxicity and adverse immune effects. Precise delivery of immunomodulators with a highly controllable system may provide a solution for this issue. Here, we developed a photocontrolled DNA nanomedicine for localized delivery of DNA immunomodulators to enhance membrane-targeted photodynamic immunotherapy. Specifically, the DNA nanomedicine is composed of long tandemly repeated functional DNA sequences (PDL1 aptamers and CpG) with a photosensitizer (TMPyP4) inserted into the DNA structure, providing high drug-loading capacity. By blocking the surface PDL1 aptamer with a pHLIP-modified cDNA, the DNA nanomedicine does not induce any obvious immune response and can be specifically delivered and anchored to the tumor membrane. Under localized irradiation, photodynamically generated reactive oxygen species (ROS) causes breakage of DNA sequences, which triggers the collapse of the nanostructure and release of internal DNA immunomodulators. Under localized illumination, photodynamically generated ROS can cause DNA sequence breaks, triggering the collapse of nanostructures and the release of internal DNA immunomodulators thus enhancing membrane-targeted photodynamic immunotherapy. We have demonstrated that the developed DNA nanomedicine can drive efficient immune responses in tumor tissue without perceptibly interfering off-tumor immunity, resulting in efficient antitumor treatment while mitigating systemic toxicity.

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A tumor acidity-driven transformable polymeric nanoassembly with deep tumor penetration and membrane-anchoring capability for targeted photodynamic therapy

Cited by 13 publications

References 36 publications

Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy

Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy

Membrane-disruptive homo-polymethacrylate with both hydrophobicity and pH-sensitive protonation for selective cancer therapy

Photocontrolled Spatiotemporal Delivery of DNA Immunomodulators for Enhancing Membrane-Targeted Tumor Photodynamic Immunotherapy

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