An upconversion nanoplatform with extracellular pH-driven tumor-targeting ability for improved photodynamic therapy

Area of Science:

• Nanomedicine
• Biotechnology
• Oncology

Background:

• Upconversion nanoparticles (UCNPs) are used in photodynamic therapy (PDT) for cancer treatment, utilizing near-infrared (NIR) light.
• Enhancing the cancer-targeting ability of nanomedicine is crucial for improving PDT efficiency.
• The pH-low insertion peptide (pHLIP) targets cancer cells in acidic tumor microenvironments.

Purpose of the Study:

• To develop and characterize a pHLIP-functionalized UCNP nanoplatform for enhanced, targeted PDT.
• To evaluate the in vitro and in vivo efficacy and safety of the pHLIP-UCNP nanoplatform.

Main Methods:

• Functionalization of 808 nm-excited UCNPs with pHLIP for active cancer targeting.
• Assembly and characterization of the pHLIP-UCNP nanoplatform.
• In vitro PDT efficacy assessment in cancer cells under varying pH conditions.
• In vivo antitumor activity evaluation and safety profiling in mice.

Main Results:

• The pHLIP-UCNP nanoplatform demonstrated efficient NIR-triggered PDT in cancer cells, particularly in acidic conditions mimicking the tumor microenvironment.
• The nanoplatform exhibited excellent tumor accumulation and significant in vivo antitumor activity upon intratumoral injection and NIR irradiation.
• Favorable safety profile with a high maximum tolerated dose (MTD) was observed in mice, alongside long bloodstream retention indicating stability.

Conclusions:

• pHLIP-functionalized UCNPs offer enhanced active targeting and efficient PDT for cancer treatment.
• The developed nanoplatform shows significant potential for in vitro and in vivo applications due to its targeting specificity, efficacy, and safety.
• This approach provides a promising strategy for developing advanced UCNP-based nanomedicines for cancer therapy.