Renal-Clearable Hollow Bismuth Subcarbonate Nanotubes for Tumor Targeted Computed Tomography Imaging and Chemoradiotherapy

Abstract

Although metallic nanomaterials with high X-ray attenuation coefficients have been widely used as X-ray computed tomography (CT) contrast agents, their intrinsically poor biodegradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance in vivo. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy. The BNTs could be targeted to tumors with high efficiency and exhibit a high CT contrast effect. Moreover, simultaneous radio- and chemotherapy using drug-loaded BNTs could significantly suppress tumor volumes, highlighting their potential application in CT imaging-guided therapy. Importantly, the elongated nanotubes could be disassembled into isolated small nanoclusters in the acidic tumor microenvironment, accelerating the payload release and kidney excretion. Such body clearable CT contrast agent with high imaging performance and multiple therapeutic functions shall have a substantial potential for biomedical applications.

Emerging Strategies of Nanomaterial‐Mediated Tumor Radiosensitization

“…Up to now, various kinds of nanoparticles formulation of radiosensitive drugs for increasing the efficacy of RT have been designed . For example, based on the effective radiosensitization effect of chemodrug CDDP, Fan et al designed rattle‐structured multifunctional upconversion core/porous silica shell nanotheranostics (UCSNs) to deliver CDDP into tumor cells for achieving chemotherapy/RT synergetic treatment .…”

Enhanced Cancer Therapy by Combining Radiation and Chemical Effects Mediated by Nanocarriers

“…who aimed at preparing hollow bismuth subcarbonate nanotubes ( Figure ). Their shape would ensure kidney clearance and less accumulation in liver and spleen, and therefore diminished toxicity . These nanotubes were successfully loaded with DOX and as they appeared to degrade at acidic pH, they were able to release encapsulated drugs.…”

“…c) TEM images of the initial Bi nanoclusters, d and e are respectively the TEM and SEM images of the fully assembles nanotubes. Adapted with permission . Copyright 2018, American Chemical Society.…”

Novel Bismuth‐Based Nanomaterials Used for Cancer Diagnosis and Therapy

“…However, considering the rapid clearance rate of quantum dots (QDs) by rental, the larger NPs are needed to realize the long circulation and allow for tumor homing, although these NPs can also be disassembled into the smaller ones at the tumor site to enhance CT imaging ability. As shown in Figure B, Hu et al . have prepared bismuth subcarbonate ((BiO) 2 CO 3 ) nanotubes (about 100 nm in length and 8 nm in diameter), which are assembled from ultrasmall (BiO) 2 CO 3 nanoclusters (≈1.5 nm).…”

“…However,c onsidering the rapid clearancer ate of quantum dots (QDs) by rental, [23] the larger NPs are neededt or ealize the long circulation and allow for tumor homing, although these NPs can also be disassembled into the smallero nes at the tumor site to enhanceC Ti maging ability.A ss hown in Figure 2B,H ue tal. [24] have prepared bismuth subcarbonate ((BiO) 2 CO 3 )n anotubes (about 100 nm in length and 8nmi nd iameter), which are assembled from ultrasmall (BiO) 2 CO 3 nanoclusters ( % 1.5 nm). The blood-elimination half-life for these nanotubes is 26.99 AE 0.41 h, about seven-times longert han that of the nanoclusters (3.77 AE 1.53 h), suggestingt hat the nanotubes offer feasible tumor accumulation ability than nanoclusters.…”