Zeolitic Imidazolate Framework‐8 as pH‐Sensitive Nanocarrier for “Arsenic Trioxide” Drug Delivery

Abstract

Previous resultsr evealed that arsenic trioxide might be used as promising therapeutic agent for the treatment of some solid tumoursa sa typical teratoid rhabdoid tumours (ATRT). However,i no rder to becomea na pproved drug for solid tumour treatment, the active formulation has to get more efficient and feasible-buta tt he same time less toxic. One of the possibilities to achieve this dichotomy is to use nanomedicine tools. Herein, we report on the Znbased metal-organicf ramework ZIF-8 (Zeolitic Imidazolate Framework-8) which turned out to be ap romising candidate for the delivery of As III species. It conjointly features ah igh drug loading capacity and ap rominent pH-triggered release behaviour.A s III -loaded ZIF-8 nanoparticlesc oated and noncoatedw ith polyethylene glycol weres tudied by XRPD, IR, Raman, TGA, TEM, EDX, CHN-elemental analysis, sorption analysisa nd ICP-OES, and their cytotoxicity was evaluated in vitro.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

“…The low therapeutic dose will avoid the possible toxicity of ZIF-8 to non-tumor cells (such as broblasts) when applied in vivo. 67 When chemotherapy is used to treat cancer, drug resistance is an important factor that hinders the effectiveness of drugs. 68 Combination medication is an effective way to block drug resistance.…”

In Vitro Studies of Fe3O4‐ZIF‐8 Core–Shell Nanoparticles Designed as Potential Theragnostics

“…ATO is bound to the structure of ZIF‐8 [Zn(C 4 N 2 H 5 ) 2 ] in a form of arsenite anions (H 2 AsO 3 − ) via a post‐synthetic ligand exchange. [ 48 ] Due to the exchange, new bands were detected at 360, 550, 660, and 710 cm −1 (Figure 2a), which corresponded to the As–OH bending, the symmetric and asymmetric mode of stretching vibrations of As(OH)₂ and As–O. [ 51 ] To further validate the exchange of the imidazolate linker to the arsenite ligand, CHN‐elemental analysis was carried out (Table S1, Supporting Information).…”

“…To evaluate the cytotoxic effects of the core–shell nanoparticles, both drug‐loaded (PEG‐NH 2 @As@Fe 3 O 4 ‐ZIF‐8) and drug free nanocarriers (PEG‐NH 2 @Fe 3 O 4 ‐ZIF‐8) were analyzed. We selected fibroblasts as non‐tumorous cells and two different atypical teratoid rhabdoid tumor (ATRT) cell lines, namely BT12 and BT16, which are known to respond positively to ATO treatment, [ 48 ] and incubated them with the tested materials in a concentration range of 0.0001–100 × 10 −6 m for 24 h and 72 h. The amount of the administrated substances was calculated with respect to the constant As‐ or Zn‐amount (Table S5, Supporting Information). After the incubation time, cell viability was measured performing a MTT assay.…”

“…[ 45 ] Recently we also contributed to the field by developing MOF based nanocarriers for ATO delivery. [ 46–48 ] In this work, we focused on developing a theragnostic agent for delivery of arsenic trioxide.…”

Applications of Simple Nanoparticle Zeolitic Imidazolate Framework-8 in Bio-medicine

“…[16] It is worth noting that in the micro-acid environment of the tumor, the pH sensitivity of ZIF-8 further satisfies the requirement for rapid release of loading drugs from nanomedicine carriers. [17][18][19][20] Utilizing these advantages, ZIF-8 nanoparticles are widely used as drug nanocarriers for delivering proteins and small-molecule chemicals ( Table 1). [21][22][23][24][25][26][27][28][29][30][31][32][33] In addition, ZIF-8 drug delivery systems are good candidates to construct the multifunctional nanoplatforms for diagnosis and treatments, and further exert its great potential in the biomedical field such as easily modified composite carriers and medical imaging.…”