Calcium phosphate nanocapsule crowned multiwalled carbon nanotubes for pH triggered intracellular anticancer drug release

Abstract

We report calcium phosphate (CaP) nanocapsule crowned multiwalled carbon nanotubes (CNT-GSH-G4-CaP) as a novel platform for intracellular delivery of an anticancer drug. As a proof-ofconcept, CNT-GSH-G4-CaP demonstrates release of anticancer drug doxorubicin hydrochloride (DOX) within intracellular lysosomes from the interior cavity of CNT upon pH triggered CaP dissolution. Importantly, we found that the CNT with a CaP nanolid can efficiently prevent untimely drug release at physiological pH but promotes DOX release at increased acidic milieu as observed in subcellular compartments such as lysosomes (B5.0). This ''zero premature release'' characteristic is of clinical significance in delivering cytotoxic drugs, by reducing systemic toxicity and thus beneficial for the effective anticancer treatment. We envision that this pH triggered CaP crowned CNT nanosystem would lead to a new generation of self-regulated platforms for intracellular delivery of a variety of anticancer drugs.

Synthesis and characterization of a multifunctional gold-doxorubicin nanoparticle system for pH triggered intracellular anticancer drug release

“…In spite of all available advanced technology for cancer treatment, chemotherapy is regularly accompanied by an off-target effect on healthy tissues and limits the dose levels of the drug below the therapeutic window to minimize patient discomfort [3]. Generally, nanoparticle based drug delivery systems are developed by the incorporation of active drugs via encapsulation, conjugation or entrapment to a nanoparticle [4][5][6].…”

“…As such PEG surface conjugation could also help to prevent adverse effects and lower the uptake of spherical AuNPs by the reticuloendothelial system (RES) during circulation in the bloodstream [23,24]. The overall efficacy of drug delivery system depends upon drug loading capacity of nanoparticles, dendrimers are useful for simultaneous conjugation drugs and targeting ligands and their structures offer the potential to increase the drug loading capacity due to its highly branched nature, 3-D spherical morphology, surface multi-functionality and well-defined composition [3,[25][26][27][28][29]. Strumina et al described the use of a nanoparticle-cored dendrimer to design platforms for drug delivery nanosystems [30], we report a novel pH-responsive PEGylated dendrimer modified drug conjugated AuNPs as a smart drug delivery system for chemotherapeutic purpose.…”

Designed Synthesis of Lipid‐Coated Polyacrylic Acid/Calcium Phosphate Nanoparticles as Dual pH‐Responsive Drug‐Delivery Vehicles for Cancer Chemotherapy

“…[4][5][6][7][8] However, problems owing to poor cellular uptake by tumor cells and inadequate intracellulard rug releasei nt umort issues still remaint o be resolved. [9,10] Based on the weakly acidic environmento ft umor tissues compared with normalp hysiological conditions, [11][12][13] various pH-responsive drug carriers have been developed to produce high intracellular drug release, such as liposomes, polymeric micelles,polymers, dendrimers, and organic/inorganic NPs. [14][15][16][17][18][19][20] Of these pH-responsive drug carriers,t he development of CaPbased nanocarriers has shown that they are potentialc andidates for intracellular drug delivery because CaP remains stable at physiologicalpH, but dissolves rapidly in an acidic endosomal( pH 5.0) or lysosomal (pH 4.5) environment, which leads to fast releaseo fa nticancerd rugs.…”

Doxorubicin Adsorbed on Carbon Nanotubes: Helical Structure and New Release Trigger

“…[18] Theoretical studies claim that small molecules with sharp and tailored pKa (6.5-5.5) are ideal for more specific release in cancerous cells, especially if the drug is loaded inside a thick multiwall carbon nanotube (MWCNT). [20] In case of Dox release from physically adsorbed Dox@CNT without any on-purpose introduced basic sites (such as chitosan) or without introduction of a Ca phosphate molecular gate, the "natural loss" of Dox at high dilution and elevated temperature has to be taken into account. [20] In case of Dox release from physically adsorbed Dox@CNT without any on-purpose introduced basic sites (such as chitosan) or without introduction of a Ca phosphate molecular gate, the "natural loss" of Dox at high dilution and elevated temperature has to be taken into account.…”