Hybrid nanostructured composite of nanocellulose and cationic starch from low-value plant biomass for local delivery of oncocalyxone A: biocompatibility, antitumor activity, and release kinetics.

Nanostructured porous composites were obtained via freeze-drying using a polymeric matrix composed of cellulose nanofibrils from Calotropis procera (NFCCp) and cationic starch from Spondias purpurea L. (CCS), crosslinked with N,N'-methylenebisacrylamide, thereby integrating low-value-added biomass valorization with their application as biomaterials for localized cancer therapy. Hollow mesoporous silica nanospheres (HMSN) loaded with oncocalyxone A (OncoA) were incorporated, achieving an encapsulation efficiency of 26.07%. The polymeric components promoted network formation through hydrogen bonding, electrostatic and covalent interactions, while the silica nanocarriers exhibited high surface area of 1703.62 m2 g-1 and a porosity of 425.31 cm3 g-1. Cytotoxicity assays demonstrated that OncoA and HMSN@OncoA were effective against leukemia (HL-60) and colorectal cancer (HCT-116) cell lines with IC50 4.42 ± 1.06 and 22.23 ± 2.46 μM respectively, without inducing in vivo toxicity in zebrafish (LC50 < 1.0 mg mL-1) or in vitro cytotoxicity in human neutrophils (2.24 ± 0.07 U L-1 at 1000 μg mL-1). The porous composites (PC) with HMSN@OncoA displayed irregular morphology of pores with heterogeneous sizes and graphitization degrees of 12.3-24.1%. Release studies indicated a non-Fickian Case II transport mechanism governed by fluid adsorption, as well as swelling and polymeric matrix relaxation, leading to the gradual migration of the OncoA from the mesopores into swollen scaffold matrix. Ex vivo evaluation using the chorioallantoic membrane assay confirmed the composites were non-irritating (66.8 to 83.4%). These results highlight that nanostructured composites based on NFCCp and CCS, incorporating HMSN@OncoA, offer a promising platform for the localized delivery of anticancer drugs following surgical resection of the affected tissue.