Biodegradable nanocomplex from hyaluronic acid and arginine based poly(ester amide)s as the delivery vehicles for improved photodynamic therapy of multidrug resistant tumor cells: An in vitro study of the performance of chlorin e6 photosensitizer

Abstract

Photodynamic therapy (PDT), which enables the localized therapeutic effect by light irradiation, provides an alternative and complementary modality for the treatment of tumor. However, the aggregation of photosensitizers in acidic microenvironment of tumor and the non-targeted distribution of photosensitizers in normal tissues significantly affect the PDT efficiency. In this study, we developed a biodegradable nanocomplex HA-Arg-PEA from hyaluronic acid (HA) and arginine based poly(ester amide)s (Arg-PEA) as the nanocarrier for chlorin e6 (Ce6). HA enhanced the tumor-specific endocytosis mediated by the overexpression of CD44 receptor. Arg-PEA not only provide electrostatic interaction with HA to form self-assembled nanostructure, but also improve the monomerization of Ce6 at physiological pH as well as mildly acidic pH. The biodegradable characteristic of HA-Arg-PEA nanocomplex enabled the intracellular delivery of Ce6, in which its release and generation of singlet oxygen can be accelerated by enzymatic degradation of the carrier. The in vitro PDT efficiency of Ce6-loaded HA-Arg-PEA nanocomplex was examined in CD44 positive MDA-MB-435/MDR multidrug resistant melanoma cells. CD44-mediated uptake of Ce6-loaded HA-Arg-PEA nanocomplex significantly improved Ce6 level in MDA-MB-435/MDR cells within short incubation time, and the PDT efficiency in inhibiting multidrug resistant tumor cells was also enhanced at higher Ce6 concentrations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1487-1499, 2017.

Multifunctional Nanoplatforms as a Novel Effective Approach in Photodynamic Therapy and Chemotherapy, to Overcome Multidrug Resistance in Cancer

“…Moreover, the intracellular level of LysoPC-BPD was maintained for up to 16 h in MCF-7 TX400 cells. This finding correlates with the observations of other authors that used pH-sensitive NPs [ 43 ] or NPs functionalized with a cell-specific marker, Annexin 1 [ 49 ] or CD44 [ 44 ]. Interestingly, similarly to silica NPs [ 33 , 51 ], poly (ADP-ribose) polymerase (PARP) cleavage [ 48 ] and cell death (apoptosis, autophagy, and oncosis) was detected after the treatment [ 46 , 48 ].With the utilization of a polymeric prodrug (PMP) encapsulated with a near infrared fluorophore (DEB-BDTO) as the PS, along with tariquidar (TQR) as an MDR inhibitor, the synergistic effect of PDT and chemotherapy was observed in SKOV-3 and SKOV-3/MDR cells.…”

“…In relation to this, the potential of other nanoplatforms was also analyzed [ 43 , 44 , 45 , 46 , 49 , 57 ] and some novel nanoplatforms were even developed [ 46 , 47 ].…”

“…In 2015, Yang et al [ 41 ] were the first to introduce multifunctional chemo-PDT and fluorescent imaging systems based on mesoporous silica NPs. Subsequently, many types of NPs and PSs were analyzed for the purpose of improving the therapeutic efficacy of PDT and chemotherapy, not only against the multidrug resistant cancer cells [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ], but also against the cancer stem cell phenotype [ 58 , 59 , 60 , 61 ].…”

Accelerate Healing of Severe Burn Wounds by Mouse Bone Marrow Mesenchymal Stem Cell-Seeded Biodegradable Hydrogel Scaffold Synthesized from Arginine-Based Poly(ester amide) and Chitosan

“…Among the amino acids for AA-PEA synthesis, arginine (Arg) is the most unique for two reasons: capable of retaining cationic charge over a wide range of pH due to its strong basic guanidine group with an isoelectric point of 10.96 and pKa above 12.5 as well as its biological property. The former character makes Arg suitable to form electrostatic nanocomplex with other negatively charged biomaterials or payloads [41][42][43][44]. Because of Arg's role in wound healing, free Arg supplement to wound patients has been suggested and reported.…”

Dual-responsive dithio-polydopamine coated porous CeO₂ nanorods for targeted and synergistic drug delivery

“…Multi-functional drug delivery systems (MDDSs) with targeting and stimulus-sensitive attributes, as an active research area, [1][2][3][4][5][6][7][8][9] can target the site of cancer cells to enhance the intracellular delivery of a drug and respond to local stimuli that are characteristic of the pathological site by shedding a protective coating and releasing entrapped drug to minimize undesired side-effect in normal cells in chemotherapy. [10][11][12] Meanwhile, degradable polymer coatings have been widely used in drug delivery systems due to their excellent drug blocking capacity and biodegradability, 13 where degradable polymers are often combined with targeting units to achieve targeted MDDS with stimuli-responsive functions which are responsive to the microenvironment of cancer cells (temperature, 14,15 pH, [16][17][18][19] glutathione (GSH) concentration, [20][21][22] or light [23][24][25] ). In addition, MDDS with enhanced cytotoxicity to cancer has been recognized as a new approach in developing a synergistic MDDS.…”