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
Highlights
Bladder cancer is the most common genitourinary malignancy in China and the second most common genitourinary malignancy in the rest of the world
Functional single-walled carbon nanotubes (SWNT) was prepared by sonication of SWNT in a phospholipid-polyethylene glycol (PEG) water solution, centrifugation, and filtration for the removal of unreacted SWNT and phospholipid-PEG
SWNT-PEG was linked to the carboxyl acid group-coupled THP through a cleavable ester
Summary
Bladder cancer is the most common genitourinary malignancy in China and the second most common genitourinary malignancy in the rest of the world. The treatment of superficial bladder cancer consists of transurethral tumor resection of visible tumors, followed by intravesical chemotherapy [1]. The response to intravesical chemotherapy is limited; up to 45% of patients with superficial bladder cancer will develop recurrent tumors, 20~30% of which progress to a higher stage or grade. Some patients fail to accept intravesical chemotherapy because of intolerance. A phase III trial showed that improving the delivery of mitomycin C nearly doubled the recurrence-free rate in superficial bladder cancer patients [2]. New drug carriers for intravesical chemotherapy need to be developed
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