Search

Highlights • HA hydrogel was prepared via hydrazone-/photo- dual crosslinking process. • HA hydrogel had topography and mechanical property similar to breast tumor tissue. • HA hydrogel promoted MCF-7 cells to cluster and secrete VEGF, bFGF and IL-8. • 3D culture enhanced cell migration and invasion potentials and in vivo tumorigenesis. Abstract In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer. [ABSTRACT FROM AUTHOR]

Highlights: [•] A novel reduction/pH dual-sensitive HA-based polymer–DOX conjugate is synthesized. [•] Hyaluronic acid–DOX conjugate can self-assemble into spherical nanoparticles (150nm). [•] The nanoparticles may release DOX rapidly in simulated intracellular environments. [•] Gal-modified nanoparticles possess good targeting ability to liver tumor. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • AHA-decorated bifunctionalized HECS-GNR conjugate was developed. • DOX was loaded onto the conjugate via hydrazone linkage. • The conjugate displayed pH-responsive surface charge reversal and drug release. • The conjugate exhibited synergetic photothermal chemotherapy of breast cancer cells. Abstract Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by chemically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Highlights • Multifunctional hyaluronic acid/hydroxyethyl chitosan nanocomplexes were prepared. • DOX and ALA were loaded into polysaccharide nanocomplexes via Schiff base linkage. • Nanocomplexes displayed pH-responsive surface charge reversal and drug release. • Active targeting enhanced additive effect of chemotherapy and photodynamic therapy. Abstract Combination of chemotherapy and photodynamic therapy has emerged as a promising anticancer strategy. Polysaccharide-based nanoparticles are being intensively explored as drug carriers for different forms of combination therapy. In this study, novel multifunctional polysaccharide-based nanocomplexes were prepared from aldehyde-functionalized hyaluronic acid and hydroxyethyl chitosan via sequential self-assembly method. Stable nanocomplexes were obtained through both Schiff's base bond and electrostatic interactions. Chemotherapeutics doxorubicin and pro-photosensitizer 5-aminolevulinic acid were chemically conjugated onto the nanocomplexes via Schiff base linkage. Anti-HER2 antibody as targeting moiety was decorated onto the surface of nanocomplexes. The obtained near-spherical shaped nanocomplexes had an average size of 140 nm and a zeta potential of −24.6 mV, and displayed pH-responsive surface charge reversal and drug release. Active targeting strategy significantly enhanced the cellular uptake of nanocomplexes and combined anticancer efficiency of chemo-photodynamic dual therapy in breast cancer MCF-7 cells. These results suggested that the nanocomplexes had great potential for targeted combination therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Hydrogels fabricated from natural polysaccharides may serve as ideal scaffolds for tissue engineering because of their similarity to the extracellular matrices. In this study, novel hydrogel scaffolds with bubble-like porous structure were prepared from hydroxyethyl chitosan (HECS) and cellulose (CEL) by a combination of chemical crosslinking, particle-leaching using silicon dioxide particles as porogen and freeze-drying method. The morphology, compression stress-strain curves, wettability, and swelling and rheological behaviors of the HECS/CEL scaffolds were characterized by SEM, mechanical test, contact angle measurement and rheometer. HECS/CEL scaffolds had good comprehensive performances and could reach equilibrium swelling state in water within 20s. The results from in vitro biocompatibility evaluated using SEM, live/dead cell viability and MTT assays demonstrated that the HECS/CEL scaffolds could well support the attachment, spreading and proliferation of osteoblastic MC3T3-E1 cells and showed good biocompatibility. Therefore, the novel HECS/CEL scaffolds may be promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics. Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles, was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma. [Display omitted] [ABSTRACT FROM AUTHOR]

• DOX/CDDP-loaded polysaccharide-based nanovehicles were successfully prepared. • CDDP crosslinking enhanced the stability of NPHER2(DOX/CDDP). • CDDP and DOX were loaded onto AHA by chelation and Schiff's base, respectively. • Nanoparticles composed of drug core and polysaccharide shell were fabricated. • Co-delivery of DOX and CDDP achieved great synergistic anticancer effect. Combination chemotherapy has attracted more and more attention in the field of anticancer treatment. Herein, a synergetic targeted combination chemotherapy of doxorubicin (DOX) and cisplatin in breast cancer was realized by HER2 antibody-decorated nanoparticles assembled from aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS). Cisplatin and DOX were successively conjugated onto AHA through chelation and Schiff's base reaction, respectively, forming DOX/cisplatin-loaded AHA inner core. The core was sequentially complexed with HECS and targeting HER2 antibody-conjugated AHA. The formed near-spherical nanoplatform had an average size of ∼160 nm and a zeta potential of −28 mV and displayed pH-responsive surface charge reversal and drug release behaviors. HER2 receptor-mediated active targeting significantly enhanced the cellular uptake of nanoplatform. Importantly, DOX and cisplatin exhibited a synergistic cell-killing effect in human breast cancer MCF-7 cells. These results clearly indicate that the novel nanoplatform is promising for synergistic combination chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]