Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy

Aim: Evaluation of the capability of Burkholderia sacchari to incorporate different monomers into polyhydroxyalkanoates (PHA). Methods and Results: Thirty different carbon sources were evaluated as cosubstrates for B. sacchari growing on glucose with the intention to promote the incorporation of different monomers into the PHA produced by this species. With odd-numbered fatty acids, incorporation of the 3HV monomer was achieved, up to 65 mol% in the case of valerate. With 4-hydroxybutyrate, incorporation of 4HB was obtained, representing 9Á1 mol%. With hexanoic acid, the production of P3HB-co-3HHx was achieved, containing up to 1Á6 mol% of 3HHx. The molar fraction of 3HHx was found to be dependent on the ratio of glucose to hexanoic acid supplied. Metabolic flux analysis revealed a high efficiency of B. sacchari in converting carbon sources into P3HB-co-3HHx. Nevertheless, hexanoic acid was only poorly converted to 3HHx. Conclusions: Burkholderia sacchari is able to incorporate 3HV, 4HB and 3HHx in PHA containing mainly 3HB. The 3HHx content of P3HB-co-3HHx can be controlled by varying the glucose to hexanoic acid ratio. Burkholderia sacchari is highly efficient in converting carbon sources into PHA; however, only 2% of the hexanoic acid supplied could be converted to 3HHx. Significance and Impact of the Study: This is the first report describing an approach to modulate the composition of P3HB-co-3HHx produced by bacteria using mixtures of carbohydrate and hexanoic acid as carbon source.

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“…; Kiliçay et al . ). Patents have indicated interest for industrial production of P3HB‐ co ‐3HHx (Noda et al .…”

Section: Discussionmentioning

confidence: 97%

Exploring the potential of Burkholderia sacchari to produce polyhydroxyalkanoates

Mendonça¹,

Gomez²,

Buffoni³

et al. 2013

J Appl Microbiol

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“…In the cytotoxicity tests, etoposide loaded and folic acid attached PHBHHX NPs were observed as more effective on HeLa cells than etoposide loaded PHBHHX NPs without attached folic acid. Furthermore the cytotoxicity of folic acid conjugated PHBHHX NPs to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the FA conjugated NPs has the ability to selectively target to cancer cells [116].…”

Section: Folate Receptormentioning

confidence: 99%

Targeted Nanoparticles for Cancer Therapy

Blanco¹,

Teijón²,

Olmo³

et al. 2012

Recent Advances in Novel Drug Carrier Systems

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“…Poly(3‐hydroxybutyrate‐ co ‐3‐hydroxyhexanoate) (PHBHHx), including its other members of polyhydroxyalkanoates (PHA) biopolyester family, has been extensively studied as a tissue engineering biomaterial and considered to be a very promising biomaterial due to its total biodegradability, non‐toxic, non‐immunogenic degradation products, and better elastic properties . PHBHHx was ever used as a biodegradable nanoparticle carrier for sustained release of hydrophobic drugs due to its hydrophobic ester backbone and alkane side chain . However, most growth factors are hydrophilic proteins and this poses a significant challenge to encapsulating not hydrophobic protein into hydrophobic PHBHHx nanoparticles efficiently.…”

Section: Introductionmentioning

confidence: 99%

Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model

Dong

Webb

Peng

et al. 2014

J. Biomed. Mater. Res.

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This study aimed to design a growth factor loaded copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) nanoparticles containing 3D collagen matrix to achieve growth factor sustained release for long-term stimulation of human mesenchymal stem cells (hMSCs) proliferation/differentiation for tissue engineer application. Platelet-derived growth factor-BB (PDGF-BB), which is known to enhance hMSCs proliferation in human serum, was selected as a model growth factor, and biodegradable copolyester of PHBHHx was chosen to be the sustained release vehicle. PDGF-BB phospholipid complex encapsulated PHBHHx nanoparticles were fabricated, and their effect on hMSCs proliferation was investigated via assays of CCK-8 and live-dead staining to cells inoculated in 2D tissue culture plates and 3D collagen gel scaffolds, respectively. The resulting spherical PHBHHx nanoparticles were stable in terms of their mean particle size, polydispersity index and zeta potential before and after lyophilization. In vitro study revealed a sustained release of PDGF-BB with a low burst release. Furthermore, sustained released PDGF-BB was revealed to significantly promote hMSCs proliferation in both cell monolayer and cell seeded 3D collagen scaffolds inoculated in serum-free media. Therefore, the 3D collagen matrices with locally sustained release growth factor nanoparticles hold promise to be used for stem cell tissue engineering.

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Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy

Cited by 89 publications

References 25 publications

Exploring the potential of Burkholderia sacchari to produce polyhydroxyalkanoates

Exploring the potential of Burkholderia sacchari to produce polyhydroxyalkanoates

Targeted Nanoparticles for Cancer Therapy

Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model

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