The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells

Abstract

Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with long-term survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanocomplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.

Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor

“…The proprietary nanodelivery system employed in SGT-53 displays exquisite specificity in delivery of payloads to tumors based on the ability of ~100 nm nanocomplex to extravasate into the tumor interstitial space and then enter tumor cells via endocytosis mediated by transferrin receptors (TfRs) that are highly elevated on tumor cells including cancer stem cells. 18 …”

A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme

“…30 In the prototype of this platform nanodelivery system, scL-p53, the wtp53 plasmid DNA payload is encapsulated within scL - a cationic liposome, the surface of which is decorated with an anti-transferrin receptor (TfR) single-chain antibody fragment (scFv) as the tumor-targeting moiety (henceforth referred to as “SGT-53”). SGT-53 is designed to target tumor cells via the TfR, which is highly expressed on surface of many tumor cells.…”

Preparation of bufalin-loaded pluronic polyetherimide nanoparticles, cellular uptake, distribution, and effect on colorectal cancer

“…17 Nanoparticulate drug delivery systems are making a significant contribution to the improvement of drug delivery in cancer. 18,19 Targeting nanoparticulate drug delivery systems, especially biodegradable nanoparticles, provides opportunities to meet these existing challenges, with the advantages of improved pharmacokinetics, favored tumor accumulation, and reduced side effects. [20][21][22] Hydrophilic pluronic polymers have a novel type of amphiphilic, nonionic surfactant micelle structure that is insoluble in the aqueous solution of the compound, which provides good solubility in the hydrophobic microenvironment, thereby increasing the solubility of water-soluble substances.…”