Abstract
Multifunctional organic/inorganic nanocomposites are highly attractive for effective biomedical applications. In this work, versatile types of self-destructible polysaccharide (dextran or pullulan) nanocomposites (denoted Au@PSa) with adjustable amounts of unlockable Au nanorods (Au NRs) were fabricated as highly efficient photothermal cancer therapy systems. Taking advantage of the acidic endosomes and high concentration of glutathione (GSH) present in cancer cells, the responsive self-destruction of Au@PSa nanocomposites could unlock the abundant encapsulated Au NRs within cells. Notably, the pullulan-based nanocomposites (denoted Au@Pul) demonstrated liver cell-targeting properties, which could enhance the therapeutic effects while minimizing side effects. The strong absorption of the unlocked Au NRs in the near-infrared region was utilized to examine the photothermal performance. The Au@PSa nanocomposites with a moderate amount of Au NRs in the matrix exhibited very impressive photothermal effects in tumor therapy, where the encapsulated Au NRs were unlocked in the tumor region to realize the observed high performance. The proposed system could be further extended, as the polysaccharides were functionalized with amino groups. The current work provides a facile strategy to construct flexible therapeutic platforms with responsive self-destruction features.
Highlights
Cancer is still a deadly disease worldwide and is the leading cause of death[1]
Au@PSa nanocomposites were synthesized by employing PSa-NH2, Au nanorods (Au NRs) with an longitudinal surface plasmon resonance (LSPR) peak at 780 nm and Ethylenediaminetetraacetic acid (EDTA) as the starting materials
With the addition of ethanol, which is a nonsolvent for both PSa and EDTA, counterion condensation of cationic PSaNH2 and anionic EDTA occurred around the Au NRs as the nucleation center[35,37]
Summary
A variety of therapeutic modalities, such as chemotherapy and photothermal therapy (PTT), have been developed to conquer the complexity of tumor and cancer metastasis[2,3,4]. Possessing tunable longitudinal surface plasmon resonance (LSPR), gold nanorods (Au NRs) demonstrate strong absorption in the desirable NIR region[29,30]. It was reported that chitosan/Au NR nanospheres possess advantages of both chitosan and Au NRs in imagingguided cancer therapy[34,35]. If more Au NRs could be loaded in one nanocapsule without severe aggregation to maintain a distinct LSPR peak in the NIR region, the relatively higher concentration of Au NRs would produce a better therapeutic performance. To explore diverse PSa types and enhance the photothermal performance, it is desirable to develop a general strategy to synthesize different kinds of PSa nanocomposites with a suitable loading amount of NRs
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