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Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use. [ABSTRACT FROM AUTHOR]

Recently, ortho‐phthalaldehyde (OPA) is experiencing a renascence for the modification of proteins and peptides through OPA‐amine two‐component reactions for bioconjugation and intramolecular OPA‐amine‐thiol three‐component reactions for cyclization. Historically, small thiol molecules were used in large excess to allow for the intermolecular OPA‐amine‐thiol reaction forming 1‐thio‐isoindole derivatives. In this study, we discovered that guanidine could serve as an effective additive to switch the intermolecular OPA‐amine‐thiol three‐component reaction to a stoichiometric process and enable the modular construction of peptide‐peptide, and peptide‐drug conjugate structures. Thus, 12 model peptide‐peptide conjugates have been synthesized from unprotected peptides featuring all proteinogenic residues. Besides, 6 peptide‐drug conjugates have been prepared in one step, with excellent conversions and isolated yields. In addition, a conjugate product has been further functionalized by utilizing a premodified OPA derivative, demonstrating the versatility and flexibility of this reaction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to find the efficient medium to bind an anticancer drug, Doxorubicin (DOX), to a synthesized polymer, methoxy poly(ethylene glycol)-block-polycaprolactone (mPEG-b-PCL) via pH sensitive hydrazone bonds and to determine the amount of conjugated drug. Methods: DOX conjugation was carried out in two different media [dimethyl sulfoxide (DMSO) and methanol-trifluoroacetic acid (MeOH-TFA)]. The amount of conjugated drug was determined with two different methods. One method was applied the dissolution of the conjugate in chloroform: methanol (Ch: MeOH, 1: 1 v/v) solution without considering pH responsiveness, and the other method was after breaking pH sensitive hydrazone bonds in acidic medium [using three different media as 0.1 M hydrochloric acid (HCl), concentrated HCl (12 M HCl) and concentrated sulfuric acid (18.3 M H2SO4)]. Results: The highest conjugation efficiency was obtained when the conjugation was achieved in MeOHTFA solution, and for the polymer-drug conjugates after the treatment with concentrated sulfuric acid. Conclusion: It was concluded that, MeOH-TFA method was a good method for conjugation of DOX to mPEG-b-PCL copolymer, and H2SO4 (18.3 M) method was better than any other present in literature for determination of the amount of DOX linked to the polymer via hydrazone conjugation. [ABSTRACT FROM AUTHOR]