Targeted delivery and apoptosis induction of CDK-4/6 inhibitor loaded folic acid decorated lipid-polymer hybrid nanoparticles in breast cancer cells

• Published in: International journal of pharmaceutics Vol. 651; p. 123787
• Main Authors: Rajana, Naveen, Sandeep Chary, Padakanti, Bhavana, Valamla, Deshmukh, Rajeshwari, Dukka, Komalatha, Sharma, Anamika, Kumar Mehra, Neelesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2024
• Subjects: Antineoplastic Agents - chemistry; Apoptosis; Breast cancer; Breast Neoplasms - drug therapy; Cell Line, Tumor; Drug Carriers - chemistry; Drug Delivery Systems - methods; Female; Folate receptor; Folic acid; Folic Acid - chemistry; Humans; Hybrid nanoparticles; In-vitro cell line studies; Lipids - pharmacology; Nanoparticles - chemistry; Palbociclib; Polymers - chemistry; CPP; FMEA; BBD; DMSO; DL; HNPs; In-vitro cell line studies; CDK; MTT; Folic acid; TFA; DSPE-PEG-FA; LPHNPs; DSC; CMA; FBS; IC50; Folate receptor; EB; EE; DCC; Palbociclib; US-FDA; AI; DAPI; 1H NMR; MW; C-6; ER; RSM; AO; QbD; BCS; AT-FTIR; ROS; DCFDA; FA; BC; NCCS; Hybrid nanoparticles; FRME; QTPP; MCF-7; CLPHNPs; FR; RPM; HER 2; DMEM; OA; ANOVA; NHS; FA-PLPHNPs; CQAs; DSPE; Breast cancer; NPs; RP-HPLC; PLGA; PI; PAL; µg/mL; DoE; TMS; RPMI; TEM; MDA-MB-231
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.123787

[Display omitted] •(FA-PLPHNPs) were fabricated by a one-step approach.•DFB-LPHNPs showed a mean particle size of 143.36 ± 05.24 nm with higher entrapment efficiency of 93.12 ± 0.43 %.•The FA-PLPHNPs exhibited approximately 8-fold higher cytotoxicity in MCF-7 and MDA-MB-231 cells at 24 h, 48 h, and 72 h.•Cell migration assay, colony formation assay, qualitative apoptosis, and quantitative apoptosis confirmed the enhanced anti-cancer activity of FA-PLPHNPs compared to Palbociclib. Targeted drug delivery is an advanced approach for active targeting of tumor that can enhance the concentration of the drug at the site of action and reduce the off-target toxicity and non-specific effects of the drug. Folate receptors (FR) are membrane-bound surface proteins, over-expressed in numerous solid tumors, folate and folate conjugates bind to FR with higher affinity. In the present investigation, we fabricated Folic acid (FA) decorated Palbociclib loaded lipid-polymer hybrid nanoparticles (FA-PLPHNPs) using quality by design (QbD) approach and evaluated its anti-cancer activity in folate receptor-positive breast cancer cell lines. 1HNMR, ATR-FTIR spectroscopic techniques confirmed the formation of DSPE-PEG-FA ligand. The optimized FA-PLPHNPs formulation exhibited 143.36 ± 5.24 nm, 0.172 ± 0.004, −16.84 ± 0.27 mV, and 93.12 ± 0.43 % of particle size, PDI, zeta potential and % entrapment efficiency, respectively. The FA-PLPHNPs exhibited an approximately 9, 11-fold reduction in IC50 values than free Palbociclib in MCF-7 and MDA-MB-231 cells at 48 h. The role of FA in targeting breast cancer was studied by means of a receptor-blocking assay, and concluded that FA-PLPHNPs were internalized into MCF-7 and MDA-MB-231 cells by folate receptor-mediated endocytosis. FA-PLPHNPs showed higher anti-cancer efficiency and caused enhanced reactive oxygen species generation, apoptosis (Acridine orange/ ethidium bromide dual staining and Annexin V/PI staining), reduced cell migration, and colony formation. Thus, the fabricated Palbociclib-loaded FA-conjugated lipid polymer hybrid nanoparticles could act as a potential nanocarrier for the treatment of breast cancer.