Nanocarriers address intracellular barriers for efficient drug delivery, overcoming drug resistance, subcellular targeting and controlled release

Liu, Jing; Cabral, Horacio; Mi, Peng

doi:10.1016/j.addr.2024.115239

Cited by 26 publications

(1 citation statement)

References 492 publications

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“…To systematically evoke adaptive immunity, nanovaccines need to be drained to lymph nodes along with carrying tumor antigens, which may compromise the needs for intravenous infusion and/or on demand drug release. However, the immunosuppressive TME provides the feasibility for stimuli-responsive nanocarrier to targeted on demand modulation by targeted delivery of immunotherapeutic eliciting both innate and adaptive antitumor immunity. − Similarly, either the passive or active targeting to tumor tissues could significantly improve the therapeutics accumulation in the TME, which provides the feasibility for immunoregulatory therapeutics delivery. − The notable distinctions between the tumor and normal tissue, such as acidic pH, altered redox potential, and upregulated enzymes, can be leveraged as the endogenous-stimuli for the design of nanomedicine. − Polymersomes, also known as polymeric vesicles, are assembled from amphiphilic block or graft copolymers and share features similar to those of liposomes, exhibiting a hollow structure surrounded by bilayer membranes that enable the delivery of nucleic acids and proteins. In addition, the higher molecular weight of polymers compared to lipids significantly enhances the mechanical properties and stability of polymersomes.…”

Section: Introductionmentioning

confidence: 99%

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment

Wei,

Weng,

Wang

et al. 2024

Biomacromolecules

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The progression of cancer involves mutations in normal cells, leading to uncontrolled division and tissue destruction, highlighting the complexity of tumor microenvironments (TMEs). Immunotherapy has emerged as a transformative approach, yet the balance between efficacy and safety remains a challenge. Nanoparticles such as polymersomes offer the possibility to precisely target tumors, deliver drugs in a controlled way, effectively modulate the antitumor immunity, and notably reduce side effects. Herein, stimuli-responsive polymersomes, with capabilities for carrying multiple therapeutics, are highlighted for their potential in enhancing antitumor immunity through mechanisms like inducing immunogenic cell death and activating STING (stimulator of interferon genes), etc. The recent progress of utilizing stimuli-responsive polymersomes to reshape the TME is reviewed here. The advantages and limitations to applied stimuli-responsive polymersomes are outlined. Additionally, challenges and future prospects in leveraging polymersomes for cancer therapy are discussed, emphasizing the need for future research and clinical translation.

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Section: Introductionmentioning

confidence: 99%

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment

Wei,

Weng,

Wang

et al. 2024

Biomacromolecules

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Size‐Tunable Boron Nanoreactors for Boron Neutron Capture Synergistic Chemodynamic Therapy of Tumor

Li,

Zhao,

Chen

et al. 2024

Adv Healthcare Materials

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Boron neutron capture therapy (BNCT) stands out as a noninvasive potential modality for invasive malignant tumors, with boron drugs playing a crucial role in its efficacy. Nevertheless, the development of boron drugs with biodegradability, as well as high permeability and retention effects, continues to present significant challenges. Here, we fabricate a size‐tunable boron nanoreactor (TBNR) via assembling boron nitride quantum dots (BNQDs) and Fe3+ for tumor BNCT and chemodynamic (CDT) synergistic treatment. The obtained TBNR with an appropriate size exhibits superior tumor accumulation and retention. Upon stimulation by the tumor microenvironment (TME), the contained Fe3+ undergo redox reactions with glutathione (GSH) to produce Fe2+ Fenton reagents, which in turn activate CDT function and simultaneously induce TBNR depolymerization. Subsequently, the released ultrasmall BNQDs exhibit intra‐deep penetration characteristic and are fully enriched at the tumor site. The in vivo experiments reveal that TBNR possesses excellent biocompatibility and superior synergistic anti‐tumor ability post neutron irradiation, resulting in significant shrinkage of subcutaneous 4T1 tumors. Moreover, the TBNR‐mediated BNCT has triggered an obvious immune response, which contributes to the long‐term suppression of tumors after neutron irradiation. To conclude, this study provides a new approach for constructing more efficient versatile nanocarriers for BNCT‐induced combination cancer therapies.

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High‐Loading L‐Arginine Stabilized in an Oxygen‐Rich Lanthanide Metal–Organic Framework Capable of NO Release and Self‐Quantifying Luminescence Detection

Xu,

Wang,

et al. 2024

Advanced Optical Materials

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Exogenous supplementation of L‐arginine (L‐Arg) facilitates the release of nitric oxide (NO) for gas therapy applications in tumor microenvironments rich in H2O2. However, direct administration inevitably leads to the premature release of hydrophilic L‐Arg in the bloodstream, potentially resulting in unstable plasma L‐Arg concentrations and subsequent adverse reactions. Therefore, it is crucial to identify efficient and stable high‐dose L‐Arg delivery carriers, albeit challenging. Here, the study has achieved high (≈94 mg g−1) and stable L‐Arg loading within a 12‐coordinated Yb‐based lanthanide metal‐organic framework (named Yb‐DOBDC, where DOBDC is 2,5‐dihydroxyterephthalic acid). Yb‐DOBDC features size‐matched apertures and oxygen‐rich pore microenvironments, securely entrapping L‐Arg through electrostatic interactions and conjugation effects, thereby enhancing the biostability of the drug during delivery. In vitro experiments demonstrate that L‐Arg‐loaded Yb‐DOBDC (L‐Arg@Yb‐DOBDC) promotes NO release upon H2O2 stimulation, and the Yb‐DOBDC framework exhibits good biocompatibility within cells. More interestingly, the near‐infrared‐luminescence‐emitting Yb‐DOBDC exhibits a “turn‐off” behavior upon gradual loading of L‐Arg, enabling self‐quantifying luminescence detection during the encapsulation process. Consequently, the L‐Arg@Yb‐DOBDC system designed in this work, with its high/stable loading capacity and self‐quantifying luminescence detection capability, holds theoretical research value and potential practical application prospects.

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Nanocarriers address intracellular barriers for efficient drug delivery, overcoming drug resistance, subcellular targeting and controlled release

Cited by 26 publications

References 492 publications

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment

Size‐Tunable Boron Nanoreactors for Boron Neutron Capture Synergistic Chemodynamic Therapy of Tumor

High‐Loading L‐Arginine Stabilized in an Oxygen‐Rich Lanthanide Metal–Organic Framework Capable of NO Release and Self‐Quantifying Luminescence Detection

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