Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Area of Science:

• Oncology
• Nanomedicine
• Biotechnology

Background:

• Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to a lack of specific molecular targets.
• Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of TNBC cases, representing a potential therapeutic target.

Purpose of the Study:

• To develop and evaluate a novel PEG engager for targeted delivery of nanomedicines to EGFR-positive (EGFR+) TNBC.
• To assess the enhanced anti-proliferative and anti-tumor activity of PEGylated nanomedicines facilitated by the PEG engager.

Main Methods:

• Design of a bifunctional PEG engager capable of binding both polyethylene glycol (PEG) and EGFR.
• In vitro assessment of the PEG engager's conditional internalization mechanism in EGFR+ TNBC cells.
• Evaluation of the anti-proliferative effects of PEG-liposomal doxorubicin in combination with the PEG engager.
• In vivo studies using human TNBC xenografts to assess drug retention and anti-tumor efficacy.

Main Results:

• The PEG engager demonstrated conditional internalization, triggering cargo engulfment upon contact with PEGylated nanocarriers.
• Enhanced anti-proliferative activity of PEG-liposomal doxorubicin against EGFR+ TNBC cells, with up to 100-fold increase in potency.
• Increased retention of PEG probes in tumors and significantly enhanced anti-tumor efficacy of PEGylated liposomal doxorubicin in vivo.
• Therapeutic efficacy was found to be dependent on EGFR expression levels.

Conclusions:

• The developed PEG engager effectively targets EGFR+ TNBC cells and enhances the therapeutic potential of PEGylated nanomedicines.
• This targeted delivery strategy offers a promising approach for improving treatment outcomes in patients with EGFR+ TNBC.