Combining hydrophilic chemotherapy and hydrophobic phytotherapy via tumor-targeted albumin–QDs nano-hybrids: covalent coupling and phospholipid complexation approaches

Abstract

BackgroundThe rationale of this study is to combine the merits of both albumin nanoparticles and quantum dots (QDs) in improved drug tumor accumulation and strong fluorescence imaging capability into one carrier. However, premature drug release from protein nanoparticles and high toxicity of QDs due to heavy metal leakage are among challenging hurdles. Following this platform, we developed cancer nano-theranostics by coupling biocompatible albumin backbone to CdTe QDs and mannose moieties to enhance tumor targeting and reduce QDs toxicity. The chemotherapeutic water soluble drug pemetrexed (PMT) was conjugated via tumor-cleavable bond to the albumin backbone for tumor site-specific release. In combination, the herbal hydrophobic drug resveratrol (RSV) was preformulated as phospholipid complex which enabled its physical encapsulation into albumin nanoparticles.ResultsAlbumin–QDs theranostics showed enhanced cytotoxicity and internalization into breast cancer cells that could be traced by virtue of their high fluorescence quantum yield and excellent imaging capacity. In vivo, the nanocarriers demonstrated superior anti-tumor effects including reduced tumor volume, increased apoptosis, and inhibited angiogenesis in addition to non-immunogenic response. Moreover, in vivo bioimaging test demonstrated excellent tumor-specific accumulation of targeted nanocarriers via QDs-mediated fluorescence.ConclusionMannose-grafted strategy and QD-fluorescence capability were beneficial to deliver albumin nanocarriers to tumor tissues and then to release the anticancer drugs for killing cancer cells as well as enabling tumor imaging facility. Overall, we believe albumin–QDs nanoplatform could be a potential nano-theranostic for bioimaging and targeted breast cancer therapy.Electronic supplementary materialThe online version of this article (10.1186/s12951-019-0445-7) contains supplementary material, which is available to authorized users.

Sequential Delivery of a Novel Triple Drug Combination via Crosslinked Alginate/lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

“…The DSC thermograms of RST revealed endothermic peaks at approximately 80°C and 164°C, which were assigned to the drug melting temperature (Fig 4A) [38]. The thermogram of PMT showed three distinctive endothermic peaks at 91.78, 153.82 and 243.80°C [39]. The characteristic peaks of RST and PMT are not observed in the PMT-ALG/LF-RST NHs F8 thermogram, which emphasizes the amorphous nature of these NHs [24].…”

The Combination of Solid-State Chemistry and Medicinal Chemistry as the Basis for the Synthesis of Theranostics Platforms

“…Silica nanoparticles containing cardioprotectors Cardiovascular diseases [11,12] PEGylated superparamagnetic iron oxide nanoparticles Liver cirrhosis [13] Amphiphilic polymer with luminogen, cyclic peptide of arginine-glycine-aspartic acid Cancer [14] PLGA lactic acid copolymer, natural RA-V cyclopeptide, fluorescent tracker, oxygen-generating agent catalase Cancer [15] Albumin nanoparticles and quantum dots, mannose fragments, pemetrexed Cancer [16] Iron oxide core with mesoporous silica shell, layer of human serum albumin, doxorubicin Cancer [17] Metal organic framework (MOF) combined with hollow mesoporous organosilica nanoparticles, indocyanine green, doxorubicin…”

“…An attempt has been made to combine the advantages of albumin nanoparticles and quantum dots (QD) to improve drug accumulation in tumors and the ability to perform strong fluorescence imaging on a single carrier [16]. Researchers have considered the problem of premature drug release from protein nanoparticles and the high toxicity of QD caused by the leakage of heavy metals.…”

Glyco-functionalised quantum dots and their progress in cancer diagnosis and treatment

“…They proved that β-galactose CdTe/CdS QDs internalised in HepG2 cells, which express asialoglycoprotein receptors, whereas α-glucose QDs showed poor uptake in HepG2 liver carcinoma cells. They later then synthesised small library of cadmium free sugar ZnS-AgInS2 QDs such as α-glucose, α-N-acetylglucose, β-galactose, mannose or [66] sialic acid [58]. They used three different cell lines, leukaemia (THP-1), macrophage (J774.A1) and HepG2 cells.…”

“…By combining the carbohydrate specific targeting towards cancer cells and strong fluorescence imaging capability of QDs, Zayed et al [66] have developed a smart cancer nano-theranostics system. The authors attached both biocompatible albumin backbone and mannose moieties to CdTe QDs for enhanced tumour targeting and reduced QDs toxicity.…”