Specific interaction between the DSPHTELP peptide and various functional groups.

M13 bacteriophages serve as a versatile foundation for nanobiotechnology due to their unique biological and chemical properties. The polypeptides that comprise their coat proteins, specifically pVIII, can be precisely tailored through genetic engineering. This enables the customized integration of various functional elements through specific interactions, leading to the development of innovative hybrid materials for applications such as energy storage, biosensing, and catalysis. Notably, a certain genetically engineered M13 bacteriophage variant, referred to as DSPH, features a pVIII with a repeating DSPHTELP peptide sequence. This sequence facilitates specific adhesion to single-walled carbon nanotubes (SWCNTs), primarily through π-π and hydrophobic interactions, though the exact mechanism remains unconfirmed. In this study, we synthesized the DSPHTELP peptide (an 8-mer peptide) and analyzed its interaction forces with different functional groups across various pH levels using surface forces apparatus (SFA). Our findings indicate that the 8-mer peptide binds most strongly to CH3 groups (Wad = 13.74 ± 1.04 mJ m-2 at pH 3.0), suggesting that hydrophobic interactions are indeed the predominant mechanism. These insights offer both quantitative and qualitative understanding of the molecular interaction mechanisms of the 8-mer peptide and clarify the basis of its specific interaction with SWCNTs through the DSPHTELP M13 bacteriophage.

Folic Acid-Functionalized ß-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer.

Recent emphasis on the design of drug delivery systems typically involves the effective transport of a pharmaceutical substance to the disease site with the desired therapeutic efficacy and minimal cytotoxicity. Organelle-targeted peptides have become an integral part of designing an important class of prodrug/prodrug assemblies for new supramolecular therapeutics owing to their favorable biocompatibility, synthetic ease, tunability of their aggregation behavior, and desired functionalization for site-specificity. However, it is still limited due to the low selectivity. We designed a folic acid-functionalized ß-cyclodextrin (FA-CD) as a delivery platform for specific and selective delivery of organelle-targeted (such as microtubule, lysosome, and mitochondria) peptide chemotherapeutics to the folate receptor (FR) overexpressing cancer cell lines. Low toxicity was found for the FA-CD and organelle-targeted peptide inclusion complex in FR-negative normal cells, but superior inhibition of tumor growth with no in vivo toxicity was found for the inclusion complex in the xenograft tumor model.

Unveiling the Power of Cloaking Metal-Organic Framework Platforms via Supramolecular Antibody Conjugation.

Targeted drug delivery systems based on metal-organic frameworks (MOFs) have progressed tremendously since inception and are now widely applicable in diverse scientific fields. However, translating MOF agents directly to targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we observed that supramolecular conjugation of antibodies to the surface of MOF particles (MOF-808) via electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments and show stealth shields. Once antibodies are stably conjugated to particles, they were neither easily exchanged with nor covered by biomolecule proteins, which is indicative of the stealth effect. Moreover, upon conjugation of the MOF particle with specific targeted antibodies, namely, anti-CD44, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR), the resulting hybrid exhibits an augmented targeting efficacy toward cancer cells overexpressing these receptors, such as HeLa, SK-BR-3, and 4T1, as evidenced by flow cytometry. The therapeutic effectiveness of the antibody-conjugated MOF (anti-M808) was further evaluated through in vivo imaging and the assessment of tumor inhibition effects using IR-780-loaded EGFR-M808 in a 4T1 tumor xenograft model employing nude mice. This study therefore provides insight into the use of supramolecular antibody conjugation as a promising method for developing MOF-based drug delivery systems.