Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here a temperature and pH dually responsive PNiPAM/AA@SiO2 core-shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2 nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), this core-shell particle has more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only PNiPAM/AA@SiO2 particles were more biocompatible and lower cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO2 had higher drug releasing efficiency in the lysosomes and stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy applications.
 ...
PMID:Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading and release with thermal and pH dually response. 2354 11

In this paper, a novel stepwise-acid-active multifunctional mesoporous silica nanoparticle (MSN-(SA)TAT&(DMA)K11) was developed as a drug carrier. The MSN-(SA)TAT&(DMA)K11 is able to reverse its surface charge from negative to positive in the mildly acidic tumor extracellular environment. Then, the fast endo/lysosomal escape and subsequent nucleus targeting as well as intranuclear drug release can be realized after cellular internalization. Because of the difference in acidity between the tumor extracellular environment and that of endo/lysosomes, this multifunctional MSN-(SA)TAT&(DMA)K11 exhibits a stepwise-acid-active drug delivery with a tumor-specific nucleus-targeted property.
...
PMID:Stepwise-acid-active multifunctional mesoporous silica nanoparticles for tumor-specific nucleus-targeted drug delivery. 2510 86

Cationic materials have been reported as promising tools for targeting to mitochondria which are the "power houses" and "metabolic garbage keepers" of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN-DTX). Once concealed by the anionic R-P shield, the assembled nanohybrid R-P@MSN-DTX will achieve prolonged blood circulation thereby leading to an enhanced EPR effect. At mildly acidic tumor environmental pH, first-stage charge reversion took place due to the hydrolysis of the amide bond on HPMA co-polymers. The de-attachment of the HPMA co-polymer occurred because of the positive charge repulsion and partial exposure of the positively charged MSN core promoted the cell internalization. The second-stage pH-responsiveness in the endo/lysosomes with a more acidic environment accelerates the disassembly of the nanohybrid and the leakage of the core facilitated the endo/lysosome escape and mitochondrial targeting with the help of intracellular compartmental acidity. Gathering up the characteristics of neutralized charge and stepwise pH-responsiveness, the R-P@MSN-DTX acquired a good tumor inhibition rate of 72.6% on nude mice. Our report provided a reference for systemic mitochondrial targeting achieved by the union of "assembly-disassembly".
 ...
PMID:A pH-responsive sequential-disassembly nanohybrid for mitochondrial targeting. 2791 Sep 90