Postoperative pain (POP) can promote tumor recurrence and reduce the cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.
The wide disparity in outcomes of
Alzheimer’s
disease (AD)
treatment from preclinical to clinical studies suggests an urgent
need for more effective therapeutic targets and approaches to treat
AD. CaMKII is a potential target for AD therapy; however, conflicting
reports on the relationship between CaMKII and AD suggest a lack of
deeper understanding of the interaction between CaMKII and AD. In
addition to the lack of effective therapeutic targets, pharmacokinetic
limitations of neuroprotective drugs, such as low lipophilicity to
cross blood brain barrier, need to be urgently addressed in the practice
of AD therapy. In this study, we prepared a carbon-based nanoparticle,
Nano C60, and demonstrated that Nano C60 treatment promoted the translocation
of phosphorylated CaMKIIα from the cytoplasm to the synapse
in Aβ42 oligomers-treated cells and APP/PS1 mice. As a result,
Nano C60 administration significantly improved spatial learning and
memory in APP/PS1 mice. Our study suggests that synaptic-activated
CaMKII may be more important than total CaMKII in AD treatment and
provides a new strategy for AD therapy.
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