Thermosensitive Nanogels with Cross-Linked Pd(II) Ions for Improving Therapeutic Effects on Platinum-Resistant Cancers via Intratumoral Formation of Hydrogels

Abstract

Although bivalent palladium [Pd(II)] compounds exhibit favorable antitumor efficacy against platinumresistant cancers, the mechanism remains unclear. Moreover, some drawbacks, such as structural lability, rapid elimination in vivo, and poor intratumoral retention, heavily limit their application in systemic tumor chemotherapy. Here, thermosensitive Pd-PNS nanogels are rationally designed by crosslinking coordination of Pd(II) ions with poly-(styrenesulfonate-b-N-isopropylacrylamide-b-styrenesulfonate) (PNS), achieving high drug-loading ability (ca. 80% of entrapment efficiency and 40% of drug-loading efficiency), sustained release, and long-term retention of highly water-soluble K 2 PdCl 4 in intratumoral administration. Cytotoxicity on sensitive/resistant MCF-7 cells and cancer stem cell (CSC) spheroids indicates that Pd-PNS nanogels could inhibit the palladium efflux of P-glycoprotein and multidrug resistance-associated protein-1 and thus enhance the DNA damage and toxicity of platinum-resistant MCF-7/Pt cells and their CSCs. Based on their temperature-sensitive sol−gel transition, Pd-PNS nanogels show sustained release profiles and long-term retention in tumors, further enhancing in vivo antitumor efficacy on MCF-7/Pt tumor-bearing BALB/c nude mice. Owing to these advantages of prolonged retention, efflux inhibition, and efficient CSCs killing ability, Pd-PNS nanogels are promising to be developed as a new temperature-sensitive delivery nanoplatform for injectable regional chemotherapy on platinum-resistant cancers.

Tailoring Aggregation Extent of Photosensitizers to Boost Phototherapy Potency for Eliciting Systemic Antitumor Immunity

“…For efficient coordination assembly, the chloride ions of cisplatin were replaced with more labile nitrate by mixing with AgNO 3 ([cisplatin]/[AgNO 3 ] = 0.5). [ 34,35 ] Pt‐ICG/PES b2 was then prepared through the coordination interaction between cisplatin and the sulfonate ligand (SO 3 − ) contained in ICG and PES. Taking Pt‐ICG/PES at a PES/ICG (PES/ICG) ratio of 6.6 (PES/ICG ratio indicated the molar ratio of SO 3 − in PES and ICG) as an example, a PESb2 aqueous solution (15 mg mL −1 , 20 mL) and ICG methanol solution (1 mg mL −1 , 10 mL) were mixed in a 50 mL round‐bottom flask under gentle stirring.…”

Phenylboronic Acid–Dopamine Dynamic Covalent Bond Involved Dual-Responsive Polymeric Complex: Construction and Anticancer Investigation

“…First, we set out to prepare a thermo- and H 2 O 2 -responsive amphiphilic copolymer, containing PNIPAM (with a lower critical solution temperature of ∼32 °C , ) as the hydrophilic block and pinacol-protected PBA- and TPE-functionalized poly­(phenyl isocyanide)­s as the hydrophobic block, by a combination of RAFT radical polymerization and Pd­(II)-initiated living polymerization. The synthetic procedure was similar to our previously reported literature and is illustrated in Figure S3a.…”

Assessment of embolization effect with temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels in rabbit renal artery by CT perfusion and pathology

“…A smart polymer material can remain in a liquid solution state at LCST and become a gelatinous solid above LCST. With a transition temperature close to physiological temperature, smart polymer materials have been reported in blood vessel embolic materials 13,16 , drug delivery [17][18][19] , precise cancer therapy 20,21 , tissue engineering 22 , and cell sheet engineering 23,24 . Most of the studies have focused on phase behaviour theory, drug delivery and promising biomedical applications.…”