Nanocarriers for targeted drug delivery in the vascular system: focus on endothelium

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 12, 2024

Endothelial cells (ECs) are pivotal in maintaining vascular health, regulating hemodynamics, and modulating inflammatory responses. Nanocarriers hold transformative potential for precise drug delivery within the system, particularly targeting ECs therapeutic purposes. However, complex interactions between nanocarriers present significant challenges development clinical translation of nanotherapeutics. This review assesses recent advancements key strategies employing to ECs. It suggested that through physicochemical design surface modifications, can enhance specificity improve internalization efficiency Additionally, we elaborated on applications specifically designed treatment cardiovascular diseases, cancer metastasis, disorders. Despite these advancements, safety concerns, complexity vivo processes, challenge achieving subcellular remain obstacles effective with nanocarriers. A comprehensive understanding endothelial cell biology its interaction is crucial realizing full targeted systems.

Language: Английский

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Modulating Intracellular Autophagy and Macropinocytosis for Increased Neighboring Drug Delivery

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Neighboring effects provided a valuable direction for in-depth penetration of nanoparticles into tumors. However, the uncontrollable drug transcytosis and limited uptake hindered by viscous cancer-associated fibroblasts (CAFs) greatly limit their penetration. Here, we proposed demonstrated that intracellular autophagosomes could carry remaining drugs to neighboring cells, enhanced macropinocytosis played major role in delivery. To enhance autophagosome-based delivery, Ca2+-doped polydopamine was prepared load GLS1 inhibitor CB-839 modified glutamine (839/CG) triggering macropinocytosis-based active cells uptake. After Ca2+-release caused lysosome damage, 839/CG escaped from lysosomes autophagosome maturation. Then, Ca2+-induced endoplasmic reticulum oscillations starvation both increased blocked autophagy flow, causing 839/CG-contained accumulation. Meanwhile, tumor its response mTOR downregulation-induced hunger, "the more you eat, hungrier get". death, were released actively ingested hungry through macropinocytosis. Combined with photothermal effect triggered CAF decrease, repeated above process Also, immunogenic death antigen presentation DCs infiltration T thereby inhibiting growth lung metastasis.

Language: Английский

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Dual Strategies Based on Golgi Apparatus/Endoplasmic Reticulum Targeting and Anchoring for High-Efficiency siRNA Delivery and Tumor RNAi Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Endolysosomal degradation of small interfering RNA (siRNA) significantly reduces the efficacy interference (RNAi) delivered by nonviral systems. Leveraging Golgi apparatus/endoplasmic reticulum (Golgi/ER) transport can help siRNA bypass endolysosomal pathway, but this approach may also result in insufficient release and an increased risk Golgi/ER-mediated exocytosis. To address these challenges, we developed two distinct strategies using a nanocomplex cell-penetrating poly(disulfide)s chondroitin sulfate, which enhances targeted internalization, transport, rapid cytoplasmic loaded siRNA. In first strategy, monensin synergy was found to enhance RNAi inhibiting both exocytosis autophagic degradation. second "directed sorting" based on KDEL peptide-mediated retrograde introduced. By conjugation peptide Golgi-to-ER promoted, reducing "random" Golgi/ER-related These operate alternatively achieve high-efficiency with significant therapeutic potential. Notably, mouse melanoma model anti-Bcl-2 siRNA, achieved tumor inhibition rates 87.1 90.1%, respectively. strategies, "targeting" "anchoring" Golgi/ER, provide potent solutions overcome challenges cellular intracellular release, efficient delivery.

Language: Английский

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Recent advances in the development of tumor microenvironment-activatable nanomotors for deep tumor penetration

Materials Today Bio, Journal Year: 2024, Volume and Issue: 27, P. 101119 - 101119

Published: June 11, 2024

Cancer represents a significant threat to human health, with the use of traditional chemotherapy drugs being limited by their harsh side effects. Tumor-targeted nanocarriers have emerged as promising solution this problem, they can deliver directly tumor site, improving drug effectiveness and reducing adverse However, efficacy most nanomedicines is hindered poor penetration into solid tumors. Nanomotors, capable converting various forms energy mechanical for self-propelled movement, offer potential enhancing delivery deep regions. External force-driven nanomotors, such those powered magnetic fields or ultrasound, provide precise control but often necessitate bulky costly external equipment. Bio-driven propelled sperm, macrophages, bacteria, utilize biological molecules self-propulsion are well-suited physiological environment. constrained lifespan, inadequate speed, immune responses. To address these issues, nanomotors been engineered propel themselves forward catalyzing intrinsic "fuel" in microenvironment. This mechanism facilitates through barriers, allowing them reach regions targeted delivery. In regard, article provides review microenvironment-activatable (fueled hydrogen peroxide, urea, arginine), discusses prospects challenges clinical translation, aiming new insights safe, efficient, treatment cancer therapy.

Language: Английский

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Multifunctional Zwitterionic N‐Oxide Polymers to Overcome Cascade Physiological Barriers for Efficient Anticancer Drug Delivery

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract For efficient anticancer drug delivery, cascade physiological barriers must be overcome, which requires the delivery vehicles to possess different or even opposite properties at stages. Poly(tertiary amine‐oxide) (PTAO) polymers with zwitterionic feature have distinct antifouling in blood circulation, can reduced and protonated hypoxic tumors promote cellular internalization. Nevertheless, effects of various PTAO structures not been studied systemically optimized. In this report, side groups are proposed optimized by modulating structures. Poly(2‐( N ‐oxide‐hexamethyleneimino)ethyl methacrylate) (POC7A) a cyclic seven‐membered ring is screened as structure for vivo applications. Moreover, block copolymer POC7A‐block‐poly( ε ‐caprolactone) (POC7A‐PCL) prepared formation micelles aqueous solution doxorubicin (DOX). The nature POC7A shells bioreductive activity protonation tumor microenvironment endows excellent long accumulation, deep penetration, effective Thus, DOX‐loaded exhibit potent antitumor efficacy after intravenous administration. Zwitterionic used nanocarriers overcome efficiently.

Language: Английский

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CD44-Targeted nanoparticles for remodeling the tumor microenvironment in a 3D Macrophage-Embedded ovarian cancer model with stem Cell-Like features

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125483 - 125483

Published: March 1, 2025

Language: Английский

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Amino acid-like “Edge” and nanozyme “Core” structured CDs for overcoming cellular uptake barrier and enhancing tumor penetration

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 512, P. 162712 - 162712

Published: April 16, 2025

Language: Английский

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Protein‐Nonfouling and Cell‐Binding Polysulfobetaine Inducing Fast Transcytosis for Tumor‐Active Drug Delivery

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 23, 2025

Abstract Long blood circulation and fast cellular uptake are essential yet paradoxical requirements for efficient tumor‐targeted drug delivery carriers. For instance, polyzwitterions, generally nonfouling to proteins cells, have been extensively explored as long‐circulating carriers but suffer ultraslow cell internalization, making them inefficient in delivering drugs cells. Protein‐resistant membrane‐binding polymers will simultaneously achieve long their designs complicated, such introducing cell‐membrane binding groups. Here, it is shown that the N ‐alkyl chain length of zwitterionic poly(sulfobetaine) can be used tune its affinity toward membranes. A with a moderately became membrane‐philic while retaining protein resistance, leading uptake, which further triggered tumor transcytosis intratumor penetration. Thus, paclitaxel (PTX)‐loaded micelles demonstrated potent antitumor efficacy triple‐negative breast cancer models. This study showcases paradigm designing polyzwitterions harmonizing properties tumor‐active

Language: Английский

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Integrating targeting and drug retention: A promising approach for cancer treatment

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 378, P. 247 - 249

Published: Dec. 14, 2024

Language: Английский

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Direct introduction of cationic and anionic lipids to create pH-sensitive charge-reversible liposomes with optimized pharmacokinetics and antitumor effects

Journal of Nanoparticle Research, Journal Year: 2024, Volume and Issue: 26(12)

Published: Dec. 1, 2024

Language: Английский

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