Polysaccharide-Gold Nanocluster Supramolecular Conjugates as a Versatile Platform for the Targeted Delivery of Anticancer Drugs

Abstract

Through the high affinity of the β-cyclodextrin (β-CD) cavity for adamantane moieties, novel polysaccharide-gold nanocluster supramolecular conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Due to their porous structure, the supramolecular conjugates could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), by taking advantage of the controlled association/dissociation of drug molecules from the cavities formed by the HACD skeletons and AuNPs cores as well as by harnessing the efficient targeting of cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs from the drug@HACD-AuNPs system was pH-responsive, with more efficient release occurring under a mildly acidic environment, such as that in a cancer cell. Taking the anticancer drug DOX as an example, cell viability experiments revealed that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess great potential for the targeted delivery of anticancer drugs.

Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions

“…using beta-cyclodextrin (β-CD) and adamantane (Ad), provide outcome282930313233. Especially when one considers that CD based host-guest interactions also play a key role in the preparation of biomedical materials and in drug delivery333435.…”

Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging

“…[65] Interestingly, few reports have recently described the unique nuclei staining properties of AuNCs, [66,67] which could allow the study of important biological processes such as mitosis. [67] This nuclei targeting is also the origin of several drug delivery studies, [68][69][70][71] such as DOX delivery via AuNC@BSA combined with two-photon imaging. [72] AuNCs were also covalently grafted on non-porous silica NPs for cytosol imaging and reactive oxygen species detection via the quenching of the gold fluorescence, [73] however, AuNCs were not combined with MSN.…”

Introduction

“…The HACDAuNPs supramolecular conjugates could serve as a platform for the controlled delivery of various anticancer drugs including doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT) by controlling the association/dissociation of drug molecules from the cavities formed by HACD and AuNPs, facilitating the efficient targeting of cancer cells via hyaluronic acid (HA). Drug-HACD-AuNPs [7]. HACD, CD-modified hyaluronic acid; AuNPs, gold nanoparticles bearing adamantane moieties; DOX, doxorubicin hydrochloride; PTX, paclitaxel; CPT, camptothecin; CPT-11, irinotecan hydrochloride; TPT, topotecan hydrochloride.…”

“…Numerous guest molecules of an appropriate size are generally able to form inclusion complexes with CDs ( Fig. 1.1) [6,7].…”