Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Abstract

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)‐poly (lactic acid)(PLA)‐folate (FA‐PEG‐PLA) was prepared in order to synthesize an active‐targeting, water‐soluble and pharmacomodulated photosensitizer nanocarrier. Drug‐loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA‐PEG‐PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA‐PEG‐PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA‐PEG‐PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR−). The enhanced uptake of HB/FA‐PEG‐PLA micelles to cancer cells resulted in a more effective post‐PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA‐PEG‐PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate‐targeted micelles in tumor‐bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20‐fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB‐loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA‐PEG‐PLA micelles have a high drug‐loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

Smart Polymeric Delivery System for Antitumor and Antimicrobial Photodynamic Therapy

“…Target tumor cells are a straightforward targeting strategy that accelerate the phagocytosis/endocytosis of nanocarriers ( Hanahan and Weinberg, 2011 ; Liu L. et al, 2016 ; Liu et al, 2017 ). The representative receptors are CD44 receptor ( Jiang et al, 2017 ), folate (FA) receptor ( Li et al, 2018d ), transferrin receptor ( Kaspler et al, 2016 ), epidermal growth factor (EGF) receptor ( del Carmen et al, 2005 ), etc.…”

Recent advances in theranostic agents based on natural products for photodynamic and sonodynamic therapy

“…Such a drug delivery system significantly increases biocompatibility, extends blood circulation of HB, and shows a good targeting antitumor activity for ovarian cancer. 53 Moreover, existing paclitaxel-encapsulated hyaluronic acid ceramide nanoparticles contain HB to achieve a combined treatment of chemotherapy and PDT. 54 Lanthanide up-conversion nanoparticles (UCNP) can absorb NIR light for UV and visible emission due to their unique step-like energy level structures (Figure 11).…”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…PIC with PS HUVEC and lung carcinoma, in vitro [46,47] poly(ethylene oxide)-block-poly(α,β-aspartic acid)/poly([5-aminopentyl]-α,β-aspartamide) -lung carcinoma, in vitro [48] poly(ethylene oxide)-block-poly(α,β-aspartic acid) PIC with PS lung carcinoma, in vitro [49] poly(N-methyl-2-vinylpyridinium iodide)-block-poly(ethylene oxide) PIC with PS - [50,51] [64] poly(oligo(ethylene oxide)methyl ether methacrylate)-block-poly(ʟ-lysine) O 2 production image-guided (FI), liver and breast cancer, in vitro [65] methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone)-benzyl degradation macrophages and endothelial cells, in vitro [40] poly(ethylene oxide)-block-poly(ε-caprolactone) degradation colon cancer and carcinoma, in vitro [37,66,67] poly(ethylene glycol)-block-poly(lactic acid) degradation [38] poly(ethylene glycol)-block-poly(ᴅ,ʟ-lactide-co-benzyl glycidyl ether) degradation macrophage and kidney cells, in vitro [45] poly(ethylene glycol)-block-poly(ε-caprolactone)-block- aliphatic polyesters, based for instance on ε-caprolactone or lactic acid [36][37][38][39][40][41]. In particular, the degradation of polyesters in vivo, a combination of both hydrolytic and enzymatic processes, makes them a first choice for the controlled delivery of drugs [42].…”

“…Folate (FA) has been extensively studied as a targeting moiety [116] due to the overexpression of folate receptors in a number of tumor types including ovarian [117] or breast cancers [118]. One of the most recent examples of FA use in PDT applications is by Li et al, where the authors have designed a FA-PEO-PLA construct to deliver hypocrellin B, a sensitizer extracted from fungi, to intraperitoneal tumors [39]. It was shown that the sensitizer concentration reached a maximum after 2 h in the targeted organs, as opposed to after at least 6-12 hours in other peritoneal organs, thereby creating a large window of opportunity for treatment with reduced side effects.…”