Biocompatible and Biodegradable Nanocarriers for Targeted Drug Delivery in Precision Medicine

Abstract

Despite the promising natural origin, biocompatibility, and biodegradability of chitosan for biomedical applications, developing biodegradable nanocarriers with controllable sizes and precise drug delivery targeting remains a significant challenge, hindering its integration into precision medicine. To address this, we synthesized gold nanocage (AuNCs)/poly-(N-isopropylacrylamide-co-carboxymethyl chitosan) core-shell multifunctional composite nanospheres (CPAu) through a two-step one-pot method. The resulting CPAu nanospheres (~146 nm in size) exhibited multi-sensitive release properties, excellent biocompatibility, and potent photothermal therapy (PTT) activity. These nanospheres effectively encapsulated diverse antitumor drugs while demonstrating triple responsiveness (thermo-, reduction-, and PTT-triggered) for targeted tumor cell delivery, thereby achieving enhanced antitumor efficacy in combinatorial chemotherapy.

Keywords: anticancer; composite nanospheres; gold nanocages; photothermal therapy; targeting delivery.

Scheme 1

Schematic representation of drug release behavior of DOX-loaded CPAu nanospheres.

Figure 1

TEM image of (A) Ag nanocubes, (B) Au nanocages and (C) CPAu nanospheres; Hydrodynamic size of (D) Ag nanocubes, (E) Au nanocages and (F) CPAu nanospheres.

Figure 2

Fe-SEM image of (A) CPAu and (B) CPAuD; (C) Zeta potential of Au, CP, CPAu and CPAuD; (D) UV/Vis spectra of CP, AuNCs, CPAu, and CPAuD.

Figure 3

(A) Photothermal conversion curves (NIR, 808 nm, 2 W cm⁻²; CP, AuNCs, and CPAu is 40 μg mL⁻¹); (B) Images taken with thermal imaging of CP, AuNCs, and CPAu aqueous solution.

Figure 4

In vitro cumulative release of DOX from CPAuD (A) at different temperatures (25, 37, and 42 °C) and (B) in the presence and absence of GSH (5 or 10 mM) in PBS buffer at 37 °C; (C) The cumulative release of CPAuD after light treatment; (D) In vitro cytotoxicity against 4T1 cells of CP, CPAu, CPAuD and CPAuD (L+) (with equivalent DOX concentration, L+: with laser treatment; ±standard deviation, n = 5).

Figure 5

At different periods, free-DOX treated the 4T1 cells image and CPAuD treated the 4T1 cells image (bar scale: 50 μm).