Eradication of Large Tumors by Nanoscale Drug Self-Assembly

Adv Mater. 2024 Dec;36(49):e2410536. doi: 10.1002/adma.202410536. Epub 2024 Oct 17.

Abstract

Most patients with cancer are first diagnosed at an advanced disease stage, when tumors are already large and/or metastases are present. This circumstance has a negative impact on the prognosis and therapeutic effect of anticancer drugs. In this study, it is demonstrated that photosensitizer chlorin e6 and the photochemotherapy drug mitoxantrone self-assemble into relatively stable nanoassemblies (CM NAs) through hydrogen-bonding effect, π-π stacking, and hydrophobic interactions. Administration of CM NAs in combination with 660 nm laser irradiation shows chemotherapeutic, photothermal, and photodynamic effects, causing tumor cell apoptosis and pyroptosis and enabling noninvasive tumor ablation without compromising the surrounding normal tissue. More importantly, treatment with CM NAs increases tumor immunogenicity, leading to a strong and long-term antitumor immune response that eradicates large tumors and provides long-term protection against tumor recurrence on various tumor models.

Keywords: large tumor; photodynamic; photothermal; pyroptosis; self‐assembly.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chlorophyllides*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Mitoxantrone / chemistry
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Photochemotherapy* / methods
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / therapeutic use
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacology
  • Porphyrins* / therapeutic use

Substances

  • phytochlorin
  • Chlorophyllides
  • Porphyrins
  • Photosensitizing Agents
  • Antineoplastic Agents
  • Mitoxantrone