PMID- 37376102 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230701 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 15 IP - 6 DP - 2023 Jun 4 TI - Mesenchymal Stem Cell Membrane-Coated TPCS(2a)-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy. LID - 10.3390/pharmaceutics15061654 [doi] LID - 1654 AB - Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS(2a)). TPCS(2a)@NPs of 98.89 +/- 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 +/- 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS(2a)@NPs, size of 139.31 +/- 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS(2a)@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS(2a)@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS(2a) in mMSC-TPCS(2a)@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen ((1)O(2)) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC(50) < 0.15 microM) and three-dimensional spheroids. FAU - Avancini, Greta AU - Avancini G AUID- ORCID: 0000-0001-8792-342X AD - Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy. FAU - Menilli, Luca AU - Menilli L AUID- ORCID: 0000-0003-2774-6411 AD - Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy. FAU - Visentin, Adele AU - Visentin A AD - Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, Italy. FAU - Milani, Celeste AU - Milani C AD - Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy. FAU - Mastrotto, Francesca AU - Mastrotto F AUID- ORCID: 0000-0002-2499-5490 AD - Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, Italy. FAU - Moret, Francesca AU - Moret F AUID- ORCID: 0000-0002-1534-3714 AD - Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy. LA - eng PT - Journal Article DEP - 20230604 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC10302938 OTO - NOTNLM OT - biomimetic nanoparticles OT - breast cancer OT - photodynamic therapy COIS- The authors declare no conflict of interest. EDAT- 2023/06/28 06:42 MHDA- 2023/06/28 06:43 PMCR- 2023/06/04 CRDT- 2023/06/28 01:37 PHST- 2023/05/03 00:00 [received] PHST- 2023/05/26 00:00 [revised] PHST- 2023/05/31 00:00 [accepted] PHST- 2023/06/28 06:43 [medline] PHST- 2023/06/28 06:42 [pubmed] PHST- 2023/06/28 01:37 [entrez] PHST- 2023/06/04 00:00 [pmc-release] AID - pharmaceutics15061654 [pii] AID - pharmaceutics-15-01654 [pii] AID - 10.3390/pharmaceutics15061654 [doi] PST - epublish SO - Pharmaceutics. 2023 Jun 4;15(6):1654. doi: 10.3390/pharmaceutics15061654.