Tumor targeted and GSH stimuli-response -lactalbumin nanotubes co-delivering doxorubicin and siRNA for cancer therapy

alpha-Lactalbumin (alpha-lac), a natural food-sourced protein, exhibits high biocompatibility as delivery systems for alpha-Lactalbumin (alpha-lac), a natural f od-sourced protein, exhibits high biocompatibility as delivery systems for small bioactive molecules or RNA. However, their potential clinical application as a delivery system is greatly liited due to the ak of targeting to desired tissues, such as tumors. Here, a delivery system/nanocarrir of small boacive molecues or RNA However, heir poential clnical applicaton as a delvery system is greatly nanotube (NT) was fabricated by the slf-assembly of peptides hydrolyzed from alpha-lac. Among the loading limited due to the lack of targeting to desired tissues, such as tumors Here, a delivery system/nanocarrier of of anti-tumor agents of doxorubicin (Dox) and siRNA, NTs were conjugated with the tLyp-1 peptide to nanotube (NT was fabr cated by the self-assembly of p ptides hydrolyzed from alpha-lac Among he loading of anti-tumor agents of doxorubicin (Dox) and siRNA, NTs were conjugated with the tLyp 1 peptde to specifically target the neuropilin 1 receptor, which exists on the membrane of MDA-MB-231 cancer cells. The micromorphology of NTs was not affected during he procsses of loading and targeting modification. specifically target the neuropilin 1 receptor, which exists on the membrane of MDA-MB-231 cancer cells Additionally, no significant changes in the size and zeta potential of the tLyp-1/NTs/Dox/siRNA nanocarrier The microm rphology of NTs was no affected du ing he processes of loading and targeting modification. were observed when stored in phosphate buffered saline for 7 days, indicaing outstanding stability. Moreover, Additionally, no significant changes in the size and zeta potential of the tLyp-1/NTs/Dox/siRNA nanocarrier both the cellular uptake efficiency and tumor accumulation effects of NTs on MDA-MB-231 breast cancer were observed when stored in phosphate buffered saline for 7 days, indicating outstanding stabilty. Moreover, cells wre significantly improved fter modifiation with tLyp-1. The relative viability of MDA-MB-231 both the cellular uptake efficiency and umor accumulation effect of NTs on MDA-MB 231 breast cancer cells was decreased by 70.1% in vitro after treatment with tLyp-1/NTs/Dox/siRNA (5 mu g/mL Dox). Finally, cells were significantly improved after modification with tLyp 1 The relative viabi ity of MDA MB-231 cells was decreased by 70 1% in vitro after treatment with tLyp-1/NTs/Dox/siRNA (5 mu g/mL Dox). Finally, a synergistic anticancer effect of Dox and siRNA co-loaded in tLyp-1/NTs was achieved in the anticancer treatment of MDA-MB-231 tumor-bearing mice. These findings indicate that food-sourced protein alpha-lac a synergistic anticancer effe t of Dox and siRNA co-loaded in tLyp-1/NT wa achieved in he anticancer nanocarriers could be used for the co-delivery of bioactive molecules and RNA, achieving synergistic and treatment of MDA-MB-231 tumor-bearing mice These findings indicate that ood-sourced protein alpha-lac nanocarriers could be used efficient therapeutic effects.(c) 2024 Beijing Academy of Food Science. Publishing services by Elsevier B.V.on behalf of KeAi Communication Co Ltd This is an open access article under the CC BY-NC-ND license .. Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http//creativecommonsorg/license /by nc nd/40/) :.--4.0. (http://creativecommonsorg/licenses/by-nc-nd/40/)