NaCl Nanoparticles as a Cancer Therapeutic

Abstract

Mammalian cells sustain low ratios of intracellular to extracellular sodium and chloride, and high ratios of potassium. [1] These asymmetric ionic gradients are critical to cell functions, driving essential cellular processes including the transport of amino acids, maintenance of cellular pH, and control of cell volume. [2] Lowering the extracellular concentrations of sodium and chloride, for instance by immersing cells in a hypotonic solution, causes cytoskeleton destruction, cell cycle arrest, and cell lysis. [3] Elevating intracellular osmolarity may induce similar effects, but it is difficult to achieve because ion transport is tightly regulated by live cells.We hypothesize that sodium chloride nanoparticles (SCNPs) can be exploited as a Trojan-horse strategy to deliver ions Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts. Herein, this preconception is challenged. The study shows that NaCl nanoparticles (SCNPs) but not salts are highly toxic to cancer cells. This is because SCNPs enter cells through endocytosis, bypassing cell regulations on ion transport. When dissolved inside cancer cells, SCNPs cause a surge of osmolarity and rapid cell lysis. Interestingly, normal cells are much more resistant to the treatment due to their relatively low sodium levels. Unlike conventional chemotherapeutics, SCNPs cause immunogenic cell death or ICD. In vivo studies show that SCNPs not only kill cancer cells, but also boost an anticancer immunity. The discovery opens up a new perspective on nanoparticle-based therapeutics.

Calcium Phosphate Mineralized Black Phosphorous with Enhanced Functionality and Anticancer Bioactivity

“…The XRD pattern of CaBPs showed that the overall crystalline structure of CaBPs was preserved because the typical diffraction peaks were consistent with those of the standard orthorhombic BP (PDF#76-1959, Figure S8, Supporting information). The Raman scattering spectrum of CaBPs showed the three prominent Raman peaks of BPs, A 1 g , B 2g , and A 2 g , [19] with slight red-shifts compared to BPs (Figure 1i). All in all, although BPs were covered by the CaP layer, CaP mineralization did not alter the overall structure and physical properties of BPs.…”

“…Based on above investigations, a key question now was finding out whether dissipation of MMP derived from direct interactions between CaBPs and cells or intracellular ionic osmolarity changes after CaBPs degradation. Mitochondria were isolated and the CaBPs signals in the mitochondria were detected by monitoring the characteristic A 1 g Raman peak of BPs. [9a,27] Obvious Raman signals were observed from CaBPs in the mitochondria after incubation for 24 h ( Figure S18a, Supporting Information).…”

“…For example, NaCl nanoparticles exhibit significant cytotoxicity in several types of cancer cells by altering the intracellular osmolarity after rapid dissolution intracellularly but cause little cytotoxicity in normal cells. [1] Some other inorganic nanoparticles such as ZnO, [2] calcium phosphate minerals, [3] and arsenene [4] have also been identified as potential anticancer agents with similar bioactivities. Considering the broad applications of nanotherapeutic platforms, the development of new nanoagents with good anticancer bioactivity is still desirable.…”

Self-Therapeutic Nanomaterials for Cancer Therapy: A Review

“…68 The NaCl nanoparticles enter the cell through endocytosis, bypassing the physiological iontransport system, and release Na + and Cl − ions inside cancer cells because of their high solubility, causing a surge of osmolarity and rapid cell lysis. 66 All of these reports could support the efforts of scientists to develop self-therapeutic nanomaterials with future applications in cancer therapy.…”

Improving Cancer Immunotherapy Outcomes Using Biomaterials

“…[78] Interestingly,N aCl nanoparticles also selectively killed tumor cells and boosted antitumor immunity. [79] Figure 7. (a) Schematic representation of an in situ sprayed bioresponsivef ibrin gel on apostsurgical tumor bed.…”