In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

Abstract

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. Key words: Single-walled carbon nanotubes; Bladder cancer; Drug vehicle; THP; Intravesical chemotherapy

Nanotechnology in Bladder Cancer: Current State of Development and Clinical Practice

“…Epirubicin-loaded poly(ethyl-2-cyanoacrylate) nanoparticles have been studied in vitro and demonstrate increased cytotoxicity, but also increased drug concentrations within superficial tissue of treated porcine bladders [27]. In addition to nanoparticles, single-walled carbon nanotubes (each ~150 nm in length) decorated with PEG and loaded them with pirarubicin demonstrated much higher drug retention within the bladder than free pirarubicin in a mouse model, and histologic examination of treated bladder tumors showed higher apoptosis rates of apoptosis than free drug [47]. …”

Carbon Nanotubes: a viable drug delivery platform for the treatment of cancer

“…Several studies have shown the degree of influence of nanoparticles size on its penetration in tumor (Huo, 2013;Hrkach et al, 2012). The size also affects the systematic distribution and the clearance of nanoparticles, smaller sizes favor excretion in the kidneys (5.5 nm cut off renal filtration) (Choi et al, 2007) and larger sizes favor metabolism by the liver (50-100 nm cut off liver filtration), or are leakage at the inter-endothelial splenic cell slits(400-500 nm) (Moghimi et al, 1991). Consequently, the size of the drug delivery nanoparticles must be between 10-100nm.…”

“…Drug vectorization by covalent bond is achieved using spacer agents as ethylenediamine, cisteamine, diaminotriethylene glycol, etc to link the drug directly to the NTC (Wu et al, 2009, Bhirde et al, 2009, Samori 2010, or the drug can be link to functionalizing agent by esterification (Chen et al, 2012, Marega et al, 2011.…”

In vitro assessment of potential bladder papillary neoplasm treatment with functionalized polyethyleneimine coated magnetic nanoparticles

“…5 Several different types of NPs have already been designed for treatment of bladder cancer, mostly to deliver chemotherapeutic drugs and other therapeutic and imaging molecules. [6][7][8][9][10][11] For targeted delivery to bladder cancer cells, different ligands have been used, such as lectins 12,13 or transferrin.…”

“…15 In vivo studies demonstrated that complexation or encapsulation of cytotoxic agents into different NPs (liposomes, polymeric NPs) can improve the efficiency of intravesical therapy. [6][7][8][9][10][11]16 Moreover, some NP formulations are already in preclinical and clinical studies. 17 Furthermore, in a recent study we have shown enhanced uptake of anionic polyacrylic acid (PAA) coated…”