Development of injectable upconversion nanoparticle‐conjugated doxorubicin theranostics electrospun nanostructure for targeted photochemotherapy in breast cancer

Abstract Nanotheranostic‐based photochemotherapies with targeted drug delivery have considerably surfaced in cancer therapy. In the presented work, polyethyleneimine‐coated upconversion nanoparticles were engineered to conjugate covalently with doxorubicin. Upconversion nanoparticles (UCNP)‐Doxorubicin (DOX)/synthesized epidermal growth factor receptor‐targeting peptide blended with polymer composite was electrospun and formulated as the injectable dosage form. The size of the UCNP and the nanofiber diameter were assessed as 26.75 ± 1.54 and 162 ± 2.82 nm, respectively. The optimized ratio of dopants resulted in UCNP photoluminescence with maximum emission intensity at around 800 nm upon 980 nm excitation wavelength. The paramagnetic nature of UCNPs and amide conjugation with the drug was confirmed analytically. The loading capacity of UCNP for doxorubicin was determined to be 54.56%, while nanofibers exhibited 98.74% capacity to encapsulate UCNP‐DOX. The release profile of UCNP‐DOX from nanofiber formulation ranged from sustained to controlled, with relative enhancement in acidic conditions. The nanofiber demonstrated good mechanical strength, robust swelling, and degradation rate. Biocompatibility tests showed more than 90% cell viability on L929 and NIH/3T3 cell lines with UCNP‐DOX@NF/pep nanoformulation. The IC50 values of 2.15 ± 0.54, 2.87 ± 0.67, and 3.42 ± 0.45 μg/mL on MDA‐MB‐231, 4T1, and MCF‐7 cancer cell line, respectively, with a significant cellular uptake, has been reported. The UCNP protruded a ≈62.7°C temperature rise within 5 min of 980 nm laser irradiation and a power density of 0.5 W cm⁻². The nanoformulation induced reactive oxygen species of 65.67% ± 3.21% and apoptosis by arresting the cell cycle sub‐G1 phase. The evaluation conveys the effectiveness of the developed injectable theranostic delivery system in cancer therapy.