Scholarlink

<p>Efficient and uniform delivery of nanomedicine into deep tumors remains challenging due to the limited targeting efficiency and the dense stromal barrier of solid tumors. Here, we report a bacterial biohybrid platform that integrates tumor-tropic bacteria with photoresponsive nanomedicine to achieve deep intratumoral drug delivery through active bacterial locomotion, passive nanoparticle diffusion, and photo-controlled spatiotemporal release. This biohybrid is constructed by conjugating attenuated <i>Salmonella typhimurium</i> VNP20009 with polyglycerol-decorated hollow mesoporous ruthenium nanoparticles, which act simultaneously as photothermal agents and nanocarriers co-encapsulating thermosensitive 1-tetradecanol and chemotherapeutic DOXorubicin. Guided by bacterial chemotaxis, the biohybrid actively colonizes the hypoxic and deep tumor regions inaccessible to conventional nanomedicines. Upon near-infrared irradiation, localized photothermal heating detaches nanoparticles from the bacterial surface, converting transport from active bacterial locomotion to passive interstitial diffusion, and simultaneously melts the thermosensitive 1-tetradecanol to trigger pulsatile doxorubicin release. Following nanoparticle detachment, the unmasked bacterial surface engages with host immune cells, promoting macrophage M1 polarization and establishing a pro‑inflammatory tumor microenvironment. This immune activation acts in concert with photothermal therapy and spatiotemporally controlled chemotherapy to synergistically achieve potent photochemo-immunotherapy with minimal systemic toxicity. Overall, this work establishes a generalizable strategy to achieve adequate intratumoral drug delivery and highlights the therapeutic potential of bacteria-mediated hybrid systems.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A biohybrid platform integrating bacterial propulsion and photoresponsive nanomedicine for adequate intratumoral drug delivery

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月7日

查看全文
  • Zhe Yu,
  • Jingwei Wang,
  • Youbei Qiao,
  • Chaoli Wang,
  • Tiehong Yang,
  • Yongan Tang,
  • Liting Chen,
  • Huabing Chen,
  • Hong Wu

摘要

Efficient and uniform delivery of nanomedicine into deep tumors remains challenging due to the limited targeting efficiency and the dense stromal barrier of solid tumors. Here, we report a bacterial biohybrid platform that integrates tumor-tropic bacteria with photoresponsive nanomedicine to achieve deep intratumoral drug delivery through active bacterial locomotion, passive nanoparticle diffusion, and photo-controlled spatiotemporal release. This biohybrid is constructed by conjugating attenuated Salmonella typhimurium VNP20009 with polyglycerol-decorated hollow mesoporous ruthenium nanoparticles, which act simultaneously as photothermal agents and nanocarriers co-encapsulating thermosensitive 1-tetradecanol and chemotherapeutic DOXorubicin. Guided by bacterial chemotaxis, the biohybrid actively colonizes the hypoxic and deep tumor regions inaccessible to conventional nanomedicines. Upon near-infrared irradiation, localized photothermal heating detaches nanoparticles from the bacterial surface, converting transport from active bacterial locomotion to passive interstitial diffusion, and simultaneously melts the thermosensitive 1-tetradecanol to trigger pulsatile doxorubicin release. Following nanoparticle detachment, the unmasked bacterial surface engages with host immune cells, promoting macrophage M1 polarization and establishing a pro‑inflammatory tumor microenvironment. This immune activation acts in concert with photothermal therapy and spatiotemporally controlled chemotherapy to synergistically achieve potent photochemo-immunotherapy with minimal systemic toxicity. Overall, this work establishes a generalizable strategy to achieve adequate intratumoral drug delivery and highlights the therapeutic potential of bacteria-mediated hybrid systems.

Graphical Abstract