Abstract
The use of phototherapy as an adjuvant bladder cancer treatment has long been considered, but its application has been severely hampered due to a lack of tumor specificity, unpredicted cytotoxicity, and insufficient anticancer efficacy. In this study, we aim to manufacture anti-EGFR indocyanine green (ICG) mitomycin C (MMC) encapsulated perfluorocarbon double nanoemulsions (EIMPDNEs), and explore their photochemotherapeutic efficacy on EGFR-expressing bladder cancer cells in vitro. The EIMPDNEs were manufactured using a double emulsification technique followed by antibody conjugation on the particles’ surfaces. The EIMPDNE were 257 ± 19.4 nm in size, with a surface charge of −12.3 ± 2.33 mV. The EGFR targetability of the EIMPNDE was confirmed by its enhanced binding efficiency to T24 cells when compared with the performance of nanodroplets without EGFR conjugation (p < 0.05). In comparison with freely dissolved ICG, the EIMPDNEs with equal ICG content conferred an improved thermal stability to the encapsulated ICG, and were able to provide a comparable hyperthermia effect and significantly enhanced the production of singlet oxygen under 808 nm near infrared (NIR) exposure with an intensity of 6 W cm−2 for 5 min (p < 0.05). Based on viability analyses, our data showed that the EIMPDNEs were effective in bladder cancer cell eradication upon NIR exposure (808 nm; 6 W cm−2), and the resulting cell death rate was even higher than that caused by a five-fold higher amount of entrapped MMC alone. With the merits of improved ICG stability, EGFR binding specificity, and effective cancer cell eradication, the EIMPDNEs exhibit potential for use in EGFR-expressing bladder cancer therapy with lower chemotoxicity.
Highlights
Urothelial cell carcinoma (UCC) remains one of the most fatal diseases of the urological system, of which bladder cancer—a lower urinary tract cancer—is the most frequently diagnosed, accounting for a very high number of deaths each year [1]
The level of fluorescence expressed from the EIMPDNEs with FS-monoclonal antibody (mAb) was 16.4-fold (p < 0.05) higher than that obtained from the FS-mAb-treated ICG-MMC-encapsulated PFC double nanoemulsions (IMPDNEs) (Figure 2III, inset image b), demonstrating that the enhanced fluorescence expression in the former group can certainly be attributed to the first-secondary antibody conjugation instead of FS-mAb adsorption on the particle surface due to electrostatic interaction and/or an imperfect wash
These results clearly show that the EIMPDNEs have an affinity to the corresponding secondary antibody molecules, indicating that the anti-epidermal growth factor receptor (EGFR)-mAbs were anchored on the EIMPDNE surface and they were able to provide an intact bioconjugation activity after the carboxyl-amine crosslinking reaction
Summary
Urothelial cell carcinoma (UCC) remains one of the most fatal diseases of the urological system, of which bladder cancer—a lower urinary tract cancer—is the most frequently diagnosed, accounting for a very high number of deaths each year [1]. More than two-thirds of newly diagnosed bladder cancers are superficial/NMIBC, these cases are usually at high risk of recurrence (50%–70%) [5], and for those who experience recurrence, 20%–40% of cases may progress to MIBC and thereafter become subject to ineffective therapeutics [6]. These circumstances indicate that an effective strategy for NMIBC therapy is still urgently needed
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