Protein-based photothermal theranostics for imaging-guided cancer therapy

Abstract

Development of imageable photothermal theranostics has attracted considerable attention for imaging guided photothermal therapy (PTT) with high tumor ablation accuracy. In this study, we strategically constructed a near-infrared (NIR) cyanine dye by introducing a rigid cyclohexenyl ring to the heptamethine chain to obtain a heptamethine dye CySCOOH with high fluorescence intensity and good stability. By covalent conjugation of CySCOOH onto human serum albumin (HSA), the as-prepared HSA@CySCOOH nanoplatform is highly efficient for NIR fluorescence/photoacoustic/thermal multimodality imaging and photothermal tumor ablation. The theranostic capability of HSA@CySCOOH was systematically evaluated both in vitro and in vivo. Most intriguingly, complete tumor elimination was achieved by intravenous injection of HSA@CySCOOH (CySCOOH, 1 mg/kg; 808 nm, 1.0 W/cm2 for 5 min) on 4T1 tumor-bearing mice, with no weight loss, noticeable toxicity, or tumor recurrence being observed. This as-prepared protein-based nanotheranostics exhibits high water dispersibility, no off target cytotoxicity, good biodegradability and biocompatibility, thus facilitating its clinical translation for cancer photothermal theranostics.

Self‐Assembled Peptide‐ and Protein‐Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy

“…Inspired by the interactions between protein molecules and drugs in vivo, protein molecules have been developed as drug delivery vehicles for photosensitizers. The conjugation of a heptamethine dye, CySCOOH, to HSA through amide coupling reaction formed HSA@CySCOOH conjugates . The conjugation induced an increase of only 1.2 nm to the size of HSA, indicating that no aggregation of HSA occurred.…”

Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy

“…Albuleukin, an albumin fusion protein with recombinant interleukin-2 that has shown promising antitumor efficacy against murine renal cell carcinoma and melanoma. 55,59 …”

“…Representative HSA drugs based on in vitro conjugation: (a) 111 In-labeled HSA for single-photon emission computed tomography (SPECT); 51 (b) Gd-labeled HSA for magnetic resonance imaging (MRI); 52 (c) 68 Ga-labeled HSA for positron emission tomography (PET); 53 (d) doxorubicin HSA conjugates for cancer chemotherapy with less side effect; 54 (e) 18 F-labeled HSA conjugates for PET; 44 (f) CysCOOH HSA conjugates for photothermal therapy; 55 (g) 3,5-diiodo-thyronine HSA conjugates for antibody production in animals; 56 (h) exendin-4 peptide HSA conjugates for the treatment of type 2 diabetes. 57 …”

BSA-assisted synthesis of ultrasmall gallic acid–Fe(III) coordination polymer nanoparticles for cancer theranostics

“…17,18 Indeed, several protein-related theranostic agents have been approved by the FDA for clinical use, including the albumin-paclitaxel NP Abraxane (nab-paclitaxel; Celgene, Summit, NJ, USA). 19,20 Therefore, the development of degradable organic and protein-related nanotheranostic agents holds great promise for clinical applications.…”