Aptamer‐Conjugated Biocompatible Nanospheres for Fluorescent Imaging–Guided Hepatocellular Carcinoma–Targeted Phototherapeutic Modality

Abstract

Conventional strategies against hepatocellular carcinoma (HCC) remain unsatisfactory due to its invasiveness and poor prognosis. Herein, it is utmost imperative to require alternative modalities with less invasiveness, good clinical efficacy, and low side effects. A combination of photothermal therapy (PTT) and photodynamic therapy (PDT) is an emerging modality against refractory HCC. To date a majority of PTT/PDT paradigms has a disappointing therapeutic efficiency, owing to low targeting ability of nanotheranostic agents or imprecise irradiation of lasers. In this study, HCC‐specific targeting aptamer and chlorine e6 (Ce6)‐modified polydopamine (PDA) nanospheres with decoration of Pt quantum dots (termed Apt‐Ce6‐PDA@Pt bioconjugates) are explored to combat HCC in vivo by synergy of PTT and PDT modalities. The Apt‐Ce6‐PDA@Pt bioconjugates can effectively accumulate into tumor sites by specifically binding Glypican‐3 (GPC3)‐positive tumor cells, and core of PDA exerts strong optical absorption in near‐infrared (NIR) region to enable photothermal performance. Meanwhile, the moieties of Ce6 subsequently serve as photosensitizers and fluorophores to generate reactive oxygen species (ROS) and guide phototherapeutics, respectively. The current study finally suggests that Apt‐Ce6‐PDA@Pt bioconjugates can act as a protocol for programmable ablation of HCC and it is believed that it will have a significant impact on clinical translation of promising therapy.

Aptamer and Peptide-Engineered Polydopamine Nanospheres for Target Delivery and Tumor Perfusion in Synergistic Chemo-Phototherapy of Pancreatic Cancer

“…We adopted SiO 2 @PDA@PTX to substitute PDA@PTX because of their similar epilayers and the quenching effect of the pure PDA core to obstruct the fluorescent visualization in agarose gel. 31 As seen in Figure 1h, the migratory signature of free aptamers suggested a strip at the molecular weight of 100 bp (lane 2) that contrasted with the DNA marker (lane 1), while the SiO 2 @PDA@PTX complex did not present any aptamer fragment smear (lane 3) owing to the aptamer's absence. Noteworthily, the SiO 2 @Apt-PDA@PTX bioconjugates almost remained where they were (lane 4) because of the big difficulty to migrate when the aptamers cross-linked to the SiO 2 @PDA@PTX precursor.…”

“…To verify the tumor-targeting specificity of aptamer-conjugated nanospheres, PL45 and PANC-1 cells were incubated with SiO 2 -FITC@PDA and SiO 2 -FITC@Apt-PDA solutions, respectively, for 6 h in dark and subsequently washed by PBS. As shown in Figure b, the cytoplasm of the cells exhibited a dim green fluorescence of FITC moieties under CLSM after the coculture of the cells with SiO 2 -FITC@PDA, and SiO 2 -FITC@PDA passively approached the periphery of the cells . Noteworthily, the cytosol of PL45 cells cocultured with SiO 2 -FITC@Apt-PDA biocomposites presented bright fluorescence emission from FITC moieties.…”

“…Then, the PDA@PTX complex (0.4 mg) was added to the NH 2 -PEG 3400 -aptamer solution. Finally, Apt-PDA@PTX was obtained after the reaction for 3 h. SiO 2 @Apt-PDA@PTX was synthesized to eliminate the quenching effect of the PDA core on the fluorescent signals, as previously reported . First of all, SiO 2 NPs were well fabricated as previously reported .…”

“…Finally, Apt-PDA@PTX was obtained after the reaction for 3 h. SiO 2 @Apt-PDA@PTX was synthesized to eliminate the quenching effect of the PDA core on the fluorescent signals, as previously reported. 31 First of all, SiO 2 NPs were well fabricated as previously reported. 32 Afterward, gel electrophoresis was employed to investigate the conjugation of anti-CD71 aptamers onto the SiO 2 @ PDA@PTX surface.…”

“…As shown in Figure 4b, the cytoplasm of the cells exhibited a dim green fluorescence of FITC moieties under CLSM after the coculture of the cells with SiO 2 -FITC@PDA, and SiO 2 -FITC@PDA passively approached the periphery of the cells. 31 Noteworthily, the cytosol of PL45 cells cocultured with SiO 2 -FITC@Apt-PDA biocomposites presented bright fluorescence emission from FITC moieties. These observations might be ascribed to the following: (i) CD71-specific targeting aptamer-modified nanospheres possessed excellent ability to target the regions of interest in PC cells; (ii) anti-CD71 aptamers mediated PC for a greater endocytic uptake of nanospheres.…”