Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Ting Wen,Yanping Fu,Xiangting Yi,Ying Sun,Wanchen Zhao,Chaonan Shi,Ziyao Chang,Beibei Yang,Shuling Li,Chao Lu,Tingting Peng,Chuanbin Wu,Xin Pan,Guilan Quan
Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO 2 bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor- β 1 (TGF- β 1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.
研究领域:
生物医学工程
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药理学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-15
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IF 10.6
Ding Ke,Tian Hailong,Li Lei,Wang Zhihan,Liu Shanshan,Ding Ning,Nice Edouard C.,Huang Canhua,Bao Jinku,Gao Wei,Shi Zheng
Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.
研究领域:
肿瘤学
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药理学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
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IF 9.6
Ling Mei,Haowei Liu,Qihang Ding,Yuxin Xie,Xue Shen,Haiyan Chen,Kaixi Wang,Man Li,Qin He
Mild photothermal therapy (mPTT) holds significant potential as a minimally invasive strategy for tumor ablation. However, its clinical translation remains constrained by the uneven intratumoral distribution of photothermal agents and the induction of autophagy pathways. These limitations frequently culminate in suboptimal therapeutic efficacy, facilitating immune evasion by residual tumor cells and thereby elevating the risk of recurrence and metastasis. Here, we report the development of nitric oxide-driven nanomotors (L-Arg-CaP@PDA-CQ) constructed by encapsulating L-arginine within calcium phosphate nanoparticles, functionalized with poly-dopamine shells and loaded with chloroquine, an autophagy inhibitor. These self-propelled nanomotors demonstrated the ability to evade lysosomal phagocytosis, penetrate vascular barriers, and enhance intratumoral accumulation. Autophagy inhibition sensitized melanoma cells to mPTT, while the combination of chloroquine with mPTT induced reactive oxygen species generation and mitochondrial disruption. Furthermore, mPTT facilitated immunogenic cell death, and chloroquine-mediated inhibition of autophagosome degradation enhanced tumor antigen presentation, stimulating robust T-cell infiltration and immune activation. This dual mechanism significantly suppressed tumor recurrence and metastasis. The proposed nanomotors provide a synergistic paradigm for augmenting mPTT and activating antitumor immunity, highlighting their translational potential in clinical oncology. Statement of Significance Mild photothermal therapy (mPTT) is a promising cancer treatment modality that operates at lower temperatures to minimize damage to healthy tissues while promoting antitumor immune responses. However, its efficacy can be limited by the activation of autophagy in tumor cells, which supports tumor survival. In addition, the hypoxic microenvironment of melanoma tumors often restricts drug penetration, further complicating treatment. To address these challenges, we have designed self-propelled smart nanomotors that can actively penetrate acidic tumor tissues and deliver drugs to the tumor site.These nanomotors modulate autophagy to enhance the sensitivity of melanoma cells to mPTT, leading to efficient tumor cell ablation.When combined with chloroquine, this approach generates large amounts of reactive oxygen species and causes mitochondrial damage, while promoting T-cell infiltration through the release of damage-associated molecular patterns (DAMPs). This strategy not only enhances the therapeutic efficacy of mPTT but also holds significant potential for clinical translation in the treatment of melanoma.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Zhen-Ming Lu,Zi-Wen Qiu,Yan-Mei Li,Ke-Yan Zhang,Ye-Yang Wu,Ni Yan,Hong Cheng
Breast cancer cells are characterized by heightened autophagy, which impairs tumor-associated antigen presentation and represents a significant barrier to the antitumor immunity. In this study, a PD-L1-targeting autophagy modulator (PFC@CQ) is fabricated to activate the photoimmunotherapy against breast cancer. Specifically, the hydrophobic photosensitizer protoporphyrin IX (PpIX) is covalently linked to the hydrophobic peptide FFVLK and a PD-L1-targeting peptide sequence CLQKTPKQC, resulting in the formation of an amphiphilic photosensitizer-peptide conjugate (PpIX-FFVLK-CLQKTPKQC, called PFC), which is capable of encapsulating the autophagy inhibitor chloroquine (CQ). PFC@CQ can not only facilitate the targeted drug codelivery to PD-L1-overexpressing breast cancer cells, but also effectively disrupt their immune evasion by blocking PD-1/PD-L1 pathway. Upon light irradiation, the photodynamic therapy (PDT) of PFC@CQ induces tumor cell destruction and immunogenic cell death (ICD), causing the release of damage-associated molecular patterns (DAMPs). Simultaneously, PFC@CQ can inhibit autophagy pathway to mediate the upregulation of MHC-I, thereby enhancing antigen presentation. This cascade immunomodulation promotes the dendritic cell maturation and CD8+ T cell activation, leading to a synergistic suppression of both primary and metastatic tumors. This work introduces an innovative autophagy modulation strategy with potent immunomodulatory capability, demonstrating a potential to trigger systemic antitumor immune responses through local treatment.
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaodi Gong,Xin Pu,Jinghai Gao,Jianhong Dang,Zhifeng Wang,Zhijun Jin,Jichang Liu,Yudong Wang,Xiaojun Liu
Considerable attention has been devoted to developing anti-cancer treatments targeted mitochondria. However, there is a dearth of literature on using luminescent metal–organic frameworks for the transportation of anti-cancer drugs to organelles. A luminescent nanotherapeutic platform known as UiO-DOX@FA/TPP has been engineered with a membrane-mitochondrial stepwise targeting strategy for the delivery of doxorubicin (DOX). DOX administration caused mitochondrial dysfunction, increased Caspase-3 activity, and cell apoptosis. The UiO-DOX@FA/TPP system improved drug sensitivity, requiring only 10.8 % of the free DOX dose. It showed strong anti-tumor effects in vivo, with over 98 % tumor growth inhibition and commendable biocompatibility. The system also enabled in vivo imaging by emitting fluorescence at around 500 nm, highlighting its transport and targeted distribution to tumor sites. Furthermore, treating cells with UiO-DOX@FA/TPP nanosystem led to extensive gene expression changes, primarily enriched in Ca 2+ signaling and autophagy regulation. The stepwise targeted luminescent UiO-DOX@FA/TPP nanosystem allow for the precise identification and delineation of ovarian cancer boundaries, monitoring of drug transport in real-time, and targeted delivery to mitochondria for inducing apoptosis. This innovative approach provides a theoretical and methodological basis for integrating ovarian cancer diagnosis and treatment.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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生物医学工程
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）