A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

Abstract

Zeolitic imidazolate framework-8 (ZIF-8) is an attractive metal organic framework (MOF) in drug delivery. Strong interaction between drugs and ZIF-8 is essential for high drug loadings through in situ construction of MOFs. However, only limited drugs with unique functional groups (COOH, SO 3 H, et al.) can interact with ZIF-8 and be encapsulated satisfactorily so far. Drugs without these functional groups are difficult to be loaded due to the lack of strong interaction. Herein a versatile prodrug strategy is proposed to solve the problems encountered by MOFs. Cytarabine (Ara) is chosen as a model drug since it cannot be loaded in ZIF-8 satisfactorily by itself. New indocyanine green (IR820) is utilized to bond with Ara for the formation of prodrug (Ara-IR820) and endows the prodrug with fluorescence imagingguided chemo-photothermal therapy, in which sulfonic groups strengthen the interaction between prodrug and ZIF-8. This prodrug loaded ZIF-8 is further functionalized with hyaluronic acid (HA) to result in active-targeting HA/ Ara-IR820@ZIF-8 nanoparticles. The in vitro and in vivo results demonstrate its excellent visual cancer therapy with tumor-targeted and pH-responsive release behavior. This design offers a new concept to solve the drug loading problem of MOFs, exhibiting a flexible strategy to expand the biomedical applications of MOFs.

ZD2‐Engineered Gold Nanostar@Metal‐Organic Framework Nanoprobes for T1‐Weighted Magnetic Resonance Imaging and Photothermal Therapy Specifically Toward Triple‐Negative Breast Cancer

“…Nanoscale MOFs are regarded as ideal nanoprobes for biomedical applications . However, in order to achieve multifunctional theranostic applications, it is desirable to synthesize MOF‐based nanocomposites by incorporating metal nanoparticles within MOF . As a typical kind of metal nanomaterial, gold nanoparticles (AuNPs) show excellent performances in surface enhanced Raman scattering imaging, photoacoustic imaging, and photothermal therapy (PTT), and are expected to have better theranostic performance by combining with MOFs.…”

Metal Organic Frameworks as Drug Targeting Delivery Vehicles in the Treatment of Cancer

“…Thus, this strategy can be exploited for early cancer diagnosis. In addition, new indocyanine green (IR820) and Cytarabine (Ara) were co-loaded in ZIF-8 by Zhang et al to achieve chemotherapy, fluorescence imaging and PTT [18]. This strategy also combined diagnosis with treatment.…”

“…Therefore, a strategy is urgently needed to compensate for this shortcoming. Zhang et al wanted to load Cytarabine (Ara) with ZIF-8, but because of the lack of a drug-acting group, it was not possible to achieve high drug loading capacity [18]. Therefore, they proposed that Cytarabine (Ara) combined with New indocyanine green (IR820) to form a prodrug together encapsulated in ZIF-8, this strategy greatly increased the drug loading capacity, which suggests Pharmaceutics 2020, 12, 232 4 of 27 that we can strengthen affinity between the carriers and the drugs by structural modification or other methods to increase the drug loading capacity of MOFs.…”

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

“…ZIF-8 could not only enableahigh drug loading capacity due to its high porosity but possibly also ap H-triggered drug released ue to the ZnÀNc oordinate bond being lesss table in acidic conditions. [21,22] This possibility of triggered releasec ould be an important add-on to the material properties in order to prepareadrug carrierfor targeted drug delivery.…”