Precise Depletion of Tumor Seed and Growing Soil with Shrinkable Nanocarrier for Potentiated Cancer Chemoimmunotherapy.

Abstract

Simultaneously targeting tumor cells and nonmalignant cells represent a more efficient strategy for replacing the traditional method of targeting only tumor cells, and co-delivery nanocarriers have inherent advantages to achieve this goal. However, differential delivery of multiple agents to various types of cell with different spatial distribution patterns remains a large challenge. Herein, we developed a nanocarrier of platinum(IV) prodrug and BLZ-945, BLZ@S-NP/Pt, to differentially target tumor cells and tumor-associated macrophages (TAMs). The BLZ@S-NP/Pt undergoes shrinkage to small platinum(IV) prodrug-conjugating nanoparticles under 660 nm light, resulting in deep tumor penetration to kill more cancer cells. Meanwhile, such shrinkage also enables the rapid release of BLZ-945 in the perivascular regions of tumor to preferentially deplete TAMs (enriched in perivascular regions). Therefore, BLZ@S-NP/Pt differentially and precisely delivers agents to TAMs and tumor cells located in different spatial distribution, respectively, eventually having synergistic anticancer effects in multiple tumor models.

• Authors: Junxia Wang, Song Shen, Jie Li, Ziyang Cao, Xianzhu Yang
• Journal: ACS nano (ACS Nano) Vol. 15 Issue 3 Pg. 4636-4646 (03 23 2021) ISSN: 1936-086X [Electronic] United States
• PMID: 33651592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Prodrugs
• Soil

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Line, Tumor
• Humans
• Immunotherapy
• Nanoparticles
• Neoplasms (drug therapy)
• Prodrugs (pharmacology, therapeutic use)
• Soil