Chemotherapy
is one of the main treatments for cancer; however,
it usually causes severe atrophy of immune organs and self-immunity
damage to patients. Human lactoferrin (hLF) is a multiple biofunctional
protein in regulating the immune response and thus holds great promise
to alleviate chemotherapy-caused immunosuppression. However, a sufficient
hLF resource and efficient delivery of hLF remain a challenge. Here,
we provide a useful strategy to simultaneously solve these two problems.
A silk sericin hydrogel system delivering recombinant hLF (SSH-rhLF)
was fabricated to alleviate the chemotherapeutic drug-caused side
effects by rhLF-carrying silk cocoons, which were cost-effectively
produced by a transgenic silkworm strain as the resource. SSH-rhLF
with a uniform porous microstructural morphology, a dominant β-sheet
internal structure, adjustable concentration and sustainable release
of the rhLF, and non-cytotoxicity properties was demonstrated. Interestingly,
the sericin hydrogel showed effective protection of the rhLF from
degradation in the stomach and small intestine, thus prolonging the
bioactivity and bioavailability of rhLF. As a result, the oral administration
of SSH-rhLF with a low rhLF dose showed significant therapeutic effects
on enhancing the immune organs of cyclophosphamide (CTX)-treated mice
by protecting the splenic follicles, promoting the expression of immunoregulatory
factors, and recovering the intestinal flora family from CTX-induced
imbalance, which were similar to those achieved by oral administration
of a high dose of free hLF in the solution form. The results suggest
that the strategy of producing rhLF silk cocoons via feeding transgenic
silkworms overcomes well the shortage of rhLF resources, improves
the bioavailability of oral rhLF, and alleviates the side effects
of chemotherapeutic drugs on immune organs. The oral SSH-rhLF will
be promising for applications in cancer chemotherapy and immunity
enhancement of patients.
With the demand for more efficient and safer therapeutic drugs, targeted therapeutic peptides are well received due to their advantages of high targeting (specificity), low immunogenicity, and minimal side effects. However, the conventional methods of screening targeted therapeutic peptides in natural proteins are tedious, time-consuming, less efficient, and require too many validation experiments, which seriously restricts the innovation and clinical development of peptide drugs. In this study, we established a novel method of screening targeted therapeutic peptides in natural proteins. We also provide details for library construction, transcription assays, receptor selection, therapeutic peptide screening, and biological activity analysis of our proposed method. This method allows us to screen the therapeutic peptides TS263 and TS1000, which have the ability to specifically promote the synthesis of the extracellular matrix. We believe that this method provides a reference for screening other drugs in natural resources, including proteins, peptides, fats, nucleic acids, and small molecules.
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