Immunomodulatory Lipocomplex Functionalized with Photosensitizer-Embedded Cancer Cell Membrane Inhibits Tumor Growth and Metastasis

Nano Lett. 2019 Aug 14;19(8):5185-5193. doi: 10.1021/acs.nanolett.9b01571. Epub 2019 Jul 16.

Abstract

Liposomes are clinically used as drug carriers for cancer therapy; however, unwanted leakage of the encapsulated anticancer drug and poor tumor-targeting efficiency of liposomes may generate toxic side effects on healthy cells and lead to failure of tumor eradication. To overcome these limitations, we functionalized liposomes with a photosensitizer (KillerRed, KR)-embedded cancer cell membrane (CCM). A lipid adjuvant was also embedded in the lipocomplex to promote the anticancer immune response. KR proteins were expressed on CCM and did not leak from the lipocomplex. Owing to the homotypic affinity of the CCM for the source cancer cells, the lipocomplex exhibited a 3.3-fold higher cancer-targeting efficiency in vivo than a control liposome. The liposome functionalized with KR-embedded CCM and lipid adjuvant generated cytotoxic reactive oxygen species in photodynamic therapy and effectively induced anticancer immune responses, inhibiting primary tumor growth and lung metastasis in homotypic tumor-bearing mice. Taken together, the lipocomplex technology may improve liposome-based cancer therapy.

Keywords: Adjuvant; cancer cell membrane; cancer immunotherapy; homotypic targeting; liposome; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane / pathology
  • Green Fluorescent Proteins / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use*
  • Liposomes / therapeutic use*
  • Mice
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Photosensitizing Agents / therapeutic use*

Substances

  • Immunologic Factors
  • Liposomes
  • Photosensitizing Agents
  • killer red protein, Anthomedusae
  • Green Fluorescent Proteins