Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Our plain-English summary of Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA, by C. Yu, Y. Zhang, N. Wang, et al (Biomaterials Research, 2022).

The study

• Authors: C. Yu, Y. Zhang, N. Wang, W. Wei, K. Cao, Q. Zhang, P. Ma, D. Xie, P. Wu, B. Liu, J. Liu, W. Xiang, X. Hu, X. Liu, J. Xie, J. Tang, Z. Long, L. Wang, H. Zeng, J. Liu
• Journal: Biomaterials Research
• Published: 2022;26(1):6
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging.

Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays.

Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5's half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/si-circPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression.

Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

© 2022. The Author(s).

In plain English

This was a laboratory and animal study testing laboratory-made (synthetic) chrysotile nanotubes (SCNTs) as a carrier for a small interfering RNA against circPRMT5 in bladder cancer. The authors made the nanotubes by hydrothermal synthesis and reported lengths of 100-200 nm, with a few more than 500 nm, an outer diameter of about 25 nm and an inner diameter of about 10 nm. Work was done in human T24 bladder cancer cells, in mice (subcutaneous xenograft and tail-vein lung metastasis models) and in MNU-treated SD rats (40 rats, 10 per group). Cell viability stayed over 85 percent with SCNTs up to 200 micrograms per millilitre. In the subcutaneous xenograft mice, the SCNTs/si-circPRMT5 group showed an 82.24 percent decrease in tumour size and an 80.44 percent decrease in tumour weight compared with PBS. In the separate tail-vein model, no visible lung metastasis was detected in mice given SCNTs/si-circPRMT5. In healthy mice injected intravenously, blood taken twenty-four hours later showed no rise in liver or kidney markers. The authors concluded the carrier delivered the siRNA efficiently and suppressed tumour growth and metastasis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro cell) and animal experiment with nanomaterial synthesis and characterisation; no human subjects
• Who was studied: Human bladder cancer T24 cells; BALB/c nude mice bearing subcutaneous T24 xenografts and a tail-vein lung metastasis model (n = 5 per group); 40 female SD rats with MNU-induced bladder tumours (10 per group); healthy mice for safety testing
• Exposure: Synthesized chrysotile nanotubes (SCNTs) made from tetraethoxysilane and magnesium chloride hexahydrate at 240 °C for 72 h, loaded with siRNA against circPRMT5 by vacuum impregnation; nanoparticles used at an SCNT:siRNA mass ratio of 20, with SCNT concentrations up to 200 micrograms per millilitre in vitro
• Main results:
  • In T24 cells, viability stayed above 85% with SCNT nanoparticles even at the highest concentration tested (200 micrograms per millilitre)
  • Gel retardation showed complete siRNA binding at an SCNT:siRNA mass ratio of 20, the ratio used for all later experiments
  • In T24 cells, SCNTs/si-circPRMT5 raised the apoptotic percentage by 43.35% compared with scrambled SCNTs and blank controls
  • In the subcutaneous mouse model, the SCNTs/si-circPRMT5 group had an 82.24% decrease in tumour size and 80.44% decrease in tumour weight compared with the PBS group; SCNTs alone and free si-circPRMT5 did not differ significantly from PBS
  • In the tail-vein lung metastasis mouse model, no visible metastasis was seen in SCNTs/si-circPRMT5 mice, while mice given SCNTs, free si-circPRMT5 or PBS showed lung metastasis
  • In the rat in situ bladder model, most tumours in the SCNTs/si-circPRMT5 group were of lower stage (pTa/T1) while most control tumours were above pT2
  • For the safety assessment, healthy mice were injected intravenously and blood was taken twenty-four hours later
  • In those healthy mice at the therapeutic dose, the authors reported no rise in serum AST, ALT, TP, TBIL, CREA or BUN compared with the PBS group
  • Tumour tissue analyses showed changes in miR-30c/SNAIL1/E-cadherin pathway members with SCNTs/si-circPRMT5, but not with SCNTs or free si-circPRMT5
• The authors' conclusion: The authors concluded that SCNTs loaded with si-circPRMT5 delivered the siRNA efficiently to bladder tumour xenografts, suppressing tumour growth and metastasis and prolonging survival, and that the approach may be suitable for clinical translation
• Limitations the authors state:
  • The authors stated that understanding of nanoparticle pharmacokinetics, including degradation and clearance, remains at an early stage
  • The authors stated that translating circRNA-targeting treatment to patients, regulating circRNA in human tumour tissue while avoiding side effects, requires further study

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Metastasis.

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