Enhanced cytotoxicity to cancer cells by mitochondria-targeting MWCNTs containing platinum(IV) prodrug of cisplatin

Mitophagy induced by nanoparticle–peptide conjugates enabling an alternative intracellular trafficking route

“…It is fundamentally critical to investigate the delivery mechanism of the nanoparticles crossing various biological barriers including cell membranes, their behaviors of intracellular trafficking, and their final fates thereof [9e11]. It has been demonstrated that peptide-conjugated nanoparticles can effectively be delivered onto the cell membrane containing targeted receptor proteins [12,13], internalized by cells [14], or further transported into the cell organelles such as nuclei [15,16] and mitochondria [17,18]. The mediation by the peptides at the nanobio interfaces is believed to play a key role in deciding the distribution or intracellular trafficking behaviors of nanoparticles [14,19].…”

Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent

“…In general, these previous studies focused on encapsulation of cisplatin or cisplatin derivatives within the lumen of CNTs as a strategy to prevent premature drug activation and for slow drug release following cell uptake. [13, 15–17] Alternatively, other CNT-based platinum chemotherapy delivery systems rely on covalent attachment to tether the functional platinum group to the CNT surface via a cleavable linker. [14, 18, 19] While these studies clearly demonstrate the capacity of using CNT for targeted drug delivery and controlled release, further clinical development may be hampered due to reliance on intracellular cleavage and modification of the platinum complex for activation, complicated linker synthesis, or inherent problems common to classical platinum pharmacophores.…”

Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

“…Specifically, mitochondrial apoptosis-inducible strategies by modifying the surface charge (ie, positive charge) of various NPs (eg, Au, liposomal, and mwCNT) are promising examples of targeting specific organelles using physiochemical materialsintracellular interactions. 91,[117][118][119][120][121] Although the safety of stem cell-based therapeutics remains controversial, engineered stem cell therapies have shown promising potential for clinical application due to their ability to search and communicate with tumor cells. 55,56,66 For example, autologous (ie, harvested and cultured from the patient) MSCs can be conjugated with specially designed nanomaterials for personalized drug therapy to effectively destroy tumor cells.…”

“…In the same manner, conjugation of rhodamine-110, a lipophilic cation, to mwCNTs significantly promoted internalization in the mitochondria of MCF-7 breast tumor cells by charge attractions and thus efficiently delivered cisplatin (platinum [IV]). 121 In summary, mitochondrial targeting by cationic NPs can enhance the therapeutic efficacy of anticancer molecules and, ultimately, initiate signal cascades by activating Bax and Bak (proteins in mitochondria that regulate apoptotic cell death). 122 …”