Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer

Abstract

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation‐enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin‐4, indicates the opening of tight junction. Moreover, MSN‐SH(E)‐associated reprogramming of M2 macrophages to M1‐like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)‐loaded nanovector (MMC@MSN‐SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN‐γ, TGF‐β1, and TNF‐α. These observations substantiated the significance of MMC@MSN‐SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

Advances in preclinical approaches for intravesical therapy of bladder cancer

“…Intravesical chemotherapy following tumor resection faces challenges in the clinical context due to the rapid degradation and elimination of chemotherapeutic drugs. A recent study generated externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) to enhance the efficiency of intravesical BC therapy [23]. The nanoparticles improved mucoadhesive properties on porcine bladders and increased permeability, as shown by the fragmented distribution of the tight junction protein claudin-4.…”

“…Furthermore, in the in vitro context, MSN-SH(E) facilitated the transformation of M2 macrophages into M1-like cells, with the mitomycin C (MMC)-loaded nanovector [MMC@MSN-SH(E)] exhibiting superior anticancer effects compared to MMC alone. Immunohistochemical analysis revealed the role of MMC@MSN-SH(E) in enhancing anticancer activity [23]. Due to their ability to adhere to mucosa, to improve permeation, to modulate the immune system and to provide prolonged drug exposure, these nanoparticles are worth further investigation as a candidate for intravesical BC therapy.…”

Application of nanotechnology in bladder cancer diagnosis and therapeutic drug delivery

“…MMC@MSN-SH(E) intervention reduced the expression of TGF-β, inhibited the proliferation and formation of tumor cells, and played an anti-cancer role. 133…”

Local Drug Delivery in Bladder Cancer: Advances of Nano/Micro/Macro-Scale Drug Delivery Systems

“…As was already mentioned, surface modification is a very popular strategy for improving tissue penetration. Surface modification of mesoporous silica nanoparticles with a second generation PAMAM dendrimers [ 67 ] or with thiols [ 68 ] ensured their enhanced mucoadhesiveness. Cell-penetrating polymer, e.g., poly(guanidinium oxanorbornene), improved the tissue penetration of modified PLGA nanoparticles by 10-fold in intravesically treated mouse bladder and ex vivo human ureter [ 69 ].…”