In situ forming alginate/gelatin hybrid hydrogels containing doxorubicin loaded chitosan/AuNPs nanogels for the local therapy of breast cancer.

In this study, pH-sensitive in situ gelling hydrogels based on oxidized alginate and gelatin-containing doxorubicin (DOX) loaded chitosan/gold nanoparticles (CS/AuNPs) nanogels were fabricated via Schiff-base bond formation. The obtained CS/AuNPs nanogels indicated a size distribution of about 209 nm with a zeta potential of +19.2 mV and an encapsulation efficiency of around 72.6 % for DOX. The study of the rheological properties of hydrogels showed that the value of G' is higher than G″ for all hydrogels, which confirms the elastic behavior of hydrogels in the applied frequency range. The rheological and texture analysis demonstrated the higher mechanical properties of hydrogels containing ß-GP and CS/AuNPs nanogels. The release profile of DOX after 48 h indicates the 99 % and 73 % release amount at pH = 5.8 and pH = 7.4, respectively. MTT cytotoxicity study showed that the prepared hydrogels are cytocompatible on MCF-7 cells. By the Live/Dead assay, it was demonstrated that the cultured cells on DOX-free hydrogels were almost alive in the presence of CS/AuNPs nanogels. However, the hydrogel-containing drug and free DOX in the same concentration caused high death of MCF-7 cells as expected, which showed the potential of the developed hydrogels for application in the local treatment of breast cancer.

Advanced nanoscale drug delivery systems for bone cancer therapy.

Bone tumors are relatively rare, which are complex cancers and primarily involve the long bones and pelvis. Bone cancer is mainly categorized into osteosarcoma (OS), chondrosarcoma, and Ewing sarcoma. Of these, OS is the most intimidating cancer of the bone tissue, which is mostly found in the log bones in young children and older adults. Conspicuously, the current chemotherapy modalities used for the treatment of OS often fail mainly due to (i) the non-specific detrimental effects on normal healthy cells/tissues, (ii) the possible emergence of drug resistance mechanisms by cancer cells, and (iii) difficulty in the efficient delivery of anticancer drugs to the target cells. To impose the maximal therapeutic impacts on cancerous cells, it is of paramount necessity to specifically deliver chemotherapeutic agents to the tumor site and target the diseased cells using advanced nanoscale multifunctional drug delivery systems (DDSs) developed using organic and inorganic nanoparticles (NPs). In this review, we provide deep insights into the development of various DDSs applied in targeting and eradicating OS. We elaborate on different DDSs developed using biomaterials, including chitosan, collagen, poly(lactic acid), poly(lactic-co-glycolic acid), polycaprolactone, poly(ethylene glycol), polyvinyl alcohol, polyethyleneimine, quantum dots, polypeptide, lipid NPs, and exosomes. We also discuss DDSs established using inorganic nanoscale materials such as magnetic NPs, gold, zinc, titanium NPs, ceramic materials, silica, silver NPs, and platinum NPs. We further highlight anticancer drugs' role in bone cancer therapy and the biocompatibility of nanocarriers for OS treatment.

Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.

Chitosan (CS)-based pH-sensitive nanocomposites were fabricated for the targeted delivery of doxorubicin (DOX) to osteosarcoma cells. To prepare the nanocomposite, CS was functionalized with succinic anhydride (SA) (CS-SA). CS-folic acid (FA) conjugates were produced by the conjugation of CS with FA via an amide bond. Next, Fe3O4 magnetic nanoparticles (MNPs) ferrofluid was fabricated, and nanocomposite was produced using MNPs and synthesized CS-SA/CS-FA and CS-SA via an inclusion formation between -COOH groups of CS-SA and hydroxyl groups of Fe3O4. Finally, DOX molecules were loaded onto the nanocomposites. The nanocomposites were characterized through FT-IR, DLS, XRD, VSM, TEM, and UV-Vis spectroscopy analyses. DOX release profile at various pHs indicated an enhanced release of DOX in acidic conditions. The cytotoxicity assay demonstrated that the nanocarriers alone were cytocompatible on cells examined. The MG-63 cells, which partly express the folate receptors (FRs), particularly FR-α, showed meaningfully higher cellular uptake of the DOX-loaded CS-FA/CS-SA@MNPs than the FR-negative lung cancer A549 cells. The DOX-loaded CS-FA/CS-SA-MNPs could induce significant cytotoxicity in the MG-63 cells but not in A549 cells. Based on these findings, the DOX-loaded CS-FA/ CS-SA-MNPs might be considered a smart pH-sensitive nanosystem for the targeted delivery of anticancer agents to osteosarcoma cancer cells.

Injectable thermosensitive hybrid hydrogel containing graphene oxide and chitosan as dental pulp stem cells scaffold for bone tissue engineering.

Here, we fabricated thermosensitive injectable hydrogel containing poly (N-isopropylacrylamide) (PNIPAAm)-based copolymer/graphene oxide (GO) composite with different feed ratio to chitosan (CS) as a natural polymer through physical and chemical crosslinking for the proliferation and differentiation of the human dental pulp stem cells (hDPSCs) to the osteoblasts. The PNIPAAm copolymer/GO composite was synthesized by free-radical copolymerization of (N-isopropylacrylamide) (NIPAAm), itaconic acid (IA) and maleic anhydride-modified poly(ethylene glycol) (PEG) in the presence of GO and used for the preparation of the hydrogels. The formulated hydrogels were evaluated for the porous architecture, rheological behavior, compressive strength, swelling property, in vitro degradation, hemocompatibility, biocompatibility, and differentiation. The hydrogel could enhance the deposition of minerals and the activity of alkaline phosphatase (ALP), in large part attributable to the oxygen and amine-containing functional groups of GO and CS. The engineered hydrogel could also upregulate the expression of the Runt-related transcription factor 2 and osteocalcin in the hDPSCs cultivated in both the normal and osteogenic media. It seems to promote the absorption of osteogenic inducer too. Based on our findings, the engineered hydrogel demonstrated the osteogenic potential, upon which it is proposed as a constructing scaffold in bone tissue engineering for the transplantation of hDPSCs.

Bioactive polymeric scaffolds for osteogenic repair and bone regenerative medicine.

The loss of bone tissue is a striking challenge in orthopedic surgery. Tissue engineering using various advanced biofunctional materials is considered a promising approach for the regeneration and substitution of impaired bone tissues. Recently, polymeric supportive scaffolds and biomaterials have been used to rationally promote the generation of new bone tissues. To restore the bone tissue in this context, biofunctional polymeric materials with significant mechanical robustness together with embedded materials can act as a supportive matrix for cellular proliferation, adhesion, and osteogenic differentiation. The osteogenic regeneration to replace defective tissues demands greater calcium deposits, high alkaline phosphatase activity, and profound upregulation of osteocalcin as a late osteogenic marker. Ideally, the bioactive polymeric scaffolds (BPSs) utilized for bone tissue engineering should impose no detrimental impacts and function as a carrier for the controlled delivery and release of the loaded molecules necessary for the bone tissue regeneration. In this review, we provide comprehensive insights into different synthetic and natural polymers used for the regeneration of bone tissue and discuss various technologies applied for the engineering of BPSs and their physicomechanical properties and biological effects.