MMP-2 sensitive poly(malic acid) micelles stabilized by π–π stacking enable high drug loading capacity

Qiao, Youbei; Zhan, Chunjing; Wang, Chaoli; Shi, Xuetao; Yang, Jing‐Fang; He, Xin; Ji, Erlong; Yu, Zhe; Yan, Changjiao; Wu, Hong

doi:10.1039/d0tb01682a

Cited by 18 publications

(15 citation statements)

References 37 publications

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“…In this study, the key product MLABn was synthesized using l -aspartic acid and l / d -malic acid ( Figure 1 ). A controlled molecular weight PMLA made from L-aspartic acid has been previously prepared by our research group [ 13 , 24 ]. The effects of temperature and reaction time on the yield of MLABn prepared using l -malic acid are presented in Table S1 .…”

Section: Resultsmentioning

confidence: 99%

“…PBM-1, which was synthesized from L-aspartic acid, has been shown to be very well biocompatible in a number of previous studies carried out by our group [ 11 , 12 , 13 , 28 ]. The crystalline PBM-2 showed disparities with PBM-1.…”

Section: Resultsmentioning

confidence: 99%

“…1 H NMR and 13 C NMR spectra were obtained on an Avance DMX-500 (Bruker, Rheinstetten, Germany) with tetramethylsilane as the internal standard. Fourier Transform Infrared Spectroscopy (FTIR) spectra were measured by FTIR-8400S (Shimadzu, Japan).…”

Section: Measurementmentioning

confidence: 99%

“…Among them, polyesters represent an attractive family because of their excellent mechanical properties, biocompatibility, and low toxicity [ 8 , 9 ]. In contrast with most common biodegradable polyesters such as polylactides or polycaprolactone, poly(β-malic acid) (PMLA) attracted our attention due to its superior physicochemical properties [ 10 , 11 , 12 , 13 ]. The hydrophilicity, plenty of modifiable carboxyl groups, and biodegradability make it a good candidate for drug carrier.…”

Section: Introductionmentioning

confidence: 99%

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Improved Synthesis of a Novel Biodegradable Tunable Micellar Polymer Based on Partially Hydrogenated Poly(β-malic Acid-co-benzyl Malate)

Ren

Qiao

et al. 2021

Molecules

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Poly(benzyl malate) (PBM), together with its derivatives, have been studied as nanocarriers for biomedical applications due to their superior biocompatibility and biodegradability. The acquisition of PBM is primarily from chemical routes, which could offer polymer-controlled molecular weight and a unique controllable morphology. Nowadays, the frequently used synthesis from L-aspartic acid gives an overall yield of 4.5%. In this work, a novel synthesis route with malic acid as the initiator was successfully designed and optimized, increasing the reaction yield up to 31.2%. Furthermore, a crystalline form of PBM (PBM-2) that polymerized from high optical purity benzyl-β-malolactonate (MLABn) was discovered during the optimization process. X-ray diffraction (XRD) patterns revealed that the crystalline PBM-2 had obvious diffraction peaks, demonstrating that its internal atoms were arranged in a more orderly manner and were different from the amorphous PBM-1 prepared from the racemic MLABn. The differential scanning calorimetry (DSC) curves and thermogravimetric curves elucidated the diverse thermal behaviors between PBM-1 and PBM-2. The degradation curves and scanning electron microscopy (SEM) images further demonstrated the biodegradability of PBM, which have different crystal structures. The hardness of PBM-2 implied the potential application in bone regeneration, while it resulted in the reduction of solubility when compared with PBM-1, which made it difficult to be dissolved and hydrogenated. The solution was therefore heated up to 75 °C to achieve benzyl deprotection, and a series of partially hydrogenated PBM was sequent prepared. Their optimal hydrogenation rates were screened to determine the optimal conditions for the formation of micelles suitable for drug-carrier applications. In summary, the synthesis route from malic acid facilitated the production of PBM for a shorter time and with a higher yield. The biodegradability, biosafety, mechanical properties, and adjustable hydrogenation widen the application of PBM with tunable properties as drug carriers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improved Synthesis of a Novel Biodegradable Tunable Micellar Polymer Based on Partially Hydrogenated Poly(β-malic Acid-co-benzyl Malate)

Ren

Qiao

et al. 2021

Molecules

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“…π–π stacking interactions between aromatic rings on the polymer chain and drug can produce a high micellar stability coupled with an improved drug loading capability. On this statement, Qiao et al [ 145 ] proposed a micelle formulation of poly(b-benzyl malate)-b-polyethylene glycol (PBM-PEG) with a loading capacity of (>20 wt%) of DOX. The systems was formulated to be target-selective, anchoring the Tat peptide to a 2 kDa PEG fragment (PBM-PEG2k-Tat).…”

Section: Polymeric Micellesmentioning

confidence: 99%

Forward Precision Medicine: Micelles for Active Targeting Driven by Peptides

et al. 2021

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Precision medicine is based on innovative administration methods of active principles. Drug delivery on tissue of interest allows improving the therapeutic index and reducing the side effects. Active targeting by means of drug-encapsulated micelles decorated with targeting bioactive moieties represents a new frontier. Between the bioactive moieties, peptides, for their versatility, easy synthesis and immunogenicity, can be selected to direct a drug toward a considerable number of molecular targets overexpressed on both cancer vasculature and cancer cells. Moreover, short peptide sequences can facilitate cellular intake. This review focuses on micelles achieved by self-assembling or mixing peptide-grafted surfactants or peptide-decorated amphiphilic copolymers. Nanovectors loaded with hydrophobic or hydrophilic cytotoxic drugs or with gene silence sequences and externally functionalized with natural or synthetic peptides are described based on their formulation and in vitro and in vivo behaviors.

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Nucleus‐Targeting Carbon Quantum Dots Assembled with Gambogic Acid via π–π Stacking for Cancer Therapy

Liu

Wang

et al. 2022

Advanced Therapeutics

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Chemotherapy combined with nanocarriers has received increased attention as a thriving strategy for tumor therapy. However, drug resistance (DR), poor circulation, and retention in cells are the main challenges of this therapy. Herein, a novel strategy is developed to target drug delivery via 𝝅-𝝅 stacking interactions to overcome DR and short circulation and retention in cells. Carbon quantum dots (CDs) and gambogic acid (GA) are assembled via a 𝝅-𝝅 stacking interaction, which increases the drug-loading capacity of CDs as well as the circulation and retention of GA-loaded CDs (CDs/GA). CDs/GA significantly inhibit cell proliferation because CDs enter the nucleus and avoid drug pump recognition. GA released from CDs/GA promotes apoptosis by inducing the production of reactive oxygen species via the mitochondrial pathway. As a result, the delivery system of CDs/GA via 𝝅-𝝅 stacking displays a significant therapeutic effect on hepatoma (HepG2) and cervical cancer (HeLa) cells. The mechanisms of DR and induction of apoptosis are further investigated. The results suggest that chemotherapy combined with CDs can facilitate the targeting of the nucleus, thereby inducing apoptosis via the mitochondrial pathway.

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MMP-2 sensitive poly(malic acid) micelles stabilized by π–π stacking enable high drug loading capacity

Abstract: Poly (β-L-malic acid) (PMLA) together with its derivatives are aliphatic polyester with superior bio-properties for anti-tumor drugs. In order to surmount the obstacle of low drug loading and rapid premature...

Cited by 18 publications

References 37 publications

Improved Synthesis of a Novel Biodegradable Tunable Micellar Polymer Based on Partially Hydrogenated Poly(β-malic Acid-co-benzyl Malate)

Improved Synthesis of a Novel Biodegradable Tunable Micellar Polymer Based on Partially Hydrogenated Poly(β-malic Acid-co-benzyl Malate)

Forward Precision Medicine: Micelles for Active Targeting Driven by Peptides

Nucleus‐Targeting Carbon Quantum Dots Assembled with Gambogic Acid via π–π Stacking for Cancer Therapy

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