Engineered polymer nanoparticles (NPs) have great potential in cancer photodynamic therapy (PDT) since they permit to locate photosensitizers, possibly coupled with another therapeutic species, at disease site and to control the release of bioactive cargo in time and space [1]. In particular, cationic nanoparticles (NPs) are at limelight in the field of cancer nanotechnology due to their unique ability to penetrate deeply inside tumor tissue [2]. Here we have developed an array of polymeric NPs based on combinations of a ionizable amino-terminated poly(?-caprolactone) (PCL-NH2) with non-ionizable polyethylenglycol-poly(?-caprolactone) (PEG-PCL) or poly(?-caprolactone) diol (PCL-OH) to attain positively charged nanoscaffolds with different charge density and surface hydrophilicity. As active drug multicargo, the lipophilic anticancer drug Docetaxel (DTX) was entrapped in the NPs core whereas anionic tetrasulfonate photosensitizers, i.e. porphyrin (TPPS4) or phthalocyanine (ZnPcS4), were adsorbed on the NPs surface. NPs below 200 nm with low polydispersity were prepared by nanoprecipitation with yields around 80%. Zeta potential could be tuned depending on the percent amount of non-ionizable PCL. DTX entrapment did not alter size and zeta potential of the nanoscaffold while adsorption extent of the negatively-charged photosensitizers was dependent on the cationic charge density on the surface. Interestingly, TPPS4 and ZnPcS4 were partly monomerized when adsorbed onto cationic NPs, depending on their composition. As a result both photosensitizers showed good response to light excitation in terms of fluorescent and photodynamic properties. Cationic NPs were stable in DMEM FBS+ while becoming negatively charged due to ion and protein interaction. To further engineer NPs surface, a top coat of Hyaluronan with low molecular weight (HA) was applied to neutralize positive charge and to encourage NPs accumulation in cancer cells overexpressing CD44 receptors. The optimized NPs carrying DTX and the photosensitizer were finally tested in cancer cells to assess the impact of surface modification on trafficking and photoactivity.
Combining photo/chemotherapy in cancer through biodegradable nanoparticles
G Dal Poggetto;P Laurienzo;
2017
Abstract
Engineered polymer nanoparticles (NPs) have great potential in cancer photodynamic therapy (PDT) since they permit to locate photosensitizers, possibly coupled with another therapeutic species, at disease site and to control the release of bioactive cargo in time and space [1]. In particular, cationic nanoparticles (NPs) are at limelight in the field of cancer nanotechnology due to their unique ability to penetrate deeply inside tumor tissue [2]. Here we have developed an array of polymeric NPs based on combinations of a ionizable amino-terminated poly(?-caprolactone) (PCL-NH2) with non-ionizable polyethylenglycol-poly(?-caprolactone) (PEG-PCL) or poly(?-caprolactone) diol (PCL-OH) to attain positively charged nanoscaffolds with different charge density and surface hydrophilicity. As active drug multicargo, the lipophilic anticancer drug Docetaxel (DTX) was entrapped in the NPs core whereas anionic tetrasulfonate photosensitizers, i.e. porphyrin (TPPS4) or phthalocyanine (ZnPcS4), were adsorbed on the NPs surface. NPs below 200 nm with low polydispersity were prepared by nanoprecipitation with yields around 80%. Zeta potential could be tuned depending on the percent amount of non-ionizable PCL. DTX entrapment did not alter size and zeta potential of the nanoscaffold while adsorption extent of the negatively-charged photosensitizers was dependent on the cationic charge density on the surface. Interestingly, TPPS4 and ZnPcS4 were partly monomerized when adsorbed onto cationic NPs, depending on their composition. As a result both photosensitizers showed good response to light excitation in terms of fluorescent and photodynamic properties. Cationic NPs were stable in DMEM FBS+ while becoming negatively charged due to ion and protein interaction. To further engineer NPs surface, a top coat of Hyaluronan with low molecular weight (HA) was applied to neutralize positive charge and to encourage NPs accumulation in cancer cells overexpressing CD44 receptors. The optimized NPs carrying DTX and the photosensitizer were finally tested in cancer cells to assess the impact of surface modification on trafficking and photoactivity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
