Multifunctional adenine-functionalized supramolecular micelles for highly selective and effective cancer chemotherapy

Ilhami, Fasih Bintang; Huang, Shan-You; Chen, Jem-Kun; Kao, Chen‐Yu; Cheng, Chih‐Chia

doi:10.1039/c9py01557d

Cited by 12 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A new low-molecular-weight supramolecular polymer micelle, adenine end-capped difunctional oligomeric A-PPG, was successfully prepared using our previously described simple, one-step synthesis [ 45 , 46 , 48 ]. To achieve a photodynamic chemotherapeutic effect, we selected 5-ALA as a photosensitizer moiety to enhance release of the chemotherapy drug DOX from the micelles at tumor sites, as presented in Scheme 1 .…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we observed low cumulative drug release (less than 28% after 96 h) from drug-loaded A-PPG micelles under physiological conditions [ 46 ]. Thus, we investigated the ability of light irradiation to induce release of DOX from DOX/5-ALA-loaded A-PPG micelles in PBS to further explore the release behavior of the system in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…Intriguingly, we discovered that these adenine-functionalized A-PPG micelles were selectively internalized into cancer cells in vitro, quickly released the encapsulated drug and significantly reduced the viability of the cancer cells. However, the same effects were not observed in healthy cells, as premature drug release was limited under normal physiological conditions [ 46 , 47 ]. Due to the existence of the self-complementary hydrogen-bonded adenine interactions, the drug-loaded micelles retained stable spherical micellar structures that restricted drug release.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the existence of the self-complementary hydrogen-bonded adenine interactions, the drug-loaded micelles retained stable spherical micellar structures that restricted drug release. At 37 °C, 19% of the drug was released in the first 24 h, 23% after 48 h, with cumulative release of only 25% after 96 h [ 46 ]. Consequently, cumulative drug release from A-PPG micelles under normal physiological conditions would be unsatisfactory for drug delivery applications.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

Ilhami

Peng

Chang

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

Ilhami

Peng

Chang

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conjugation of polymers with targeting agents such as aptamers, antibody, folic acid, and proteins improve the tumor target ability in co-therapy [81,82]. Aptamers produced from nucleic acids, RNA, or DNA specifically bind to a ligand, like a cancer antigen, for targeting cancer cells [83].…”

Section: Drug Deliverymentioning

confidence: 99%

Functionalization of Polymers and Nanomaterials for Biomedical Applications: Antimicrobial Platforms and Drug Carriers

et al. 2020

View full text Add to dashboard Cite

The use of polymers and nanomaterials has vastly grown for industrial and biomedical sectors during last years. Before any designation or selection of polymers and their nanocomposites, it is vital to recognize the targeted applications which require these platforms to be modified. Surface functionalization to introduce the desired type and quantity of reactive functional groups to target a cell or tissue in human body is a pivotal approach to improve the physicochemical and biological properties of these materials. Herein, advances in the functionalized polymer and nanomaterials surfaces are highlighted along with their applications in biomedical fields, e.g., antimicrobial therapy and drug delivery.

show abstract

Adenine‐Functionalized Supramolecular Micelles for Selective Cancer Chemotherapy

Ilhami

Alemayehu

Fan

et al. 2020

Macromolecular Bioscience

Self Cite

View full text Add to dashboard Cite

Functional supramolecular micelles containing self‐complementary multiple hydrogen bonding adenine groups (A‐PPG) can spontaneously self‐assemble into stable nanosized micelles in aqueous solution. These micelles can be used to selectively deliver anticancer drugs to cancer cells and effectively promote tumor cell death via apoptosis, without harming normal cells. The drug‐loaded micelles exhibit tunable drug‐loading capacity and rapid pH‐triggered drug release under acidic conditions, as well as a high drug‐entrapment stability in serum‐rich media due to the reversible hydrogen‐bonded adenine–adenine interactions within the micellar interior; these properties are critical to achieving effective chemotherapeutic drug delivery and controlled drug release. In vitro assays show that the drug‐loaded micelles exert significant cytotoxic effects on cancer cells, with minimal effects on normal cells under physiological conditions. Cytotoxicity assays using A‐PPG micelles loaded with different anticancer drugs confirm these effects. Importantly, cellular internalization and flow cytometric analyses demonstrate that the adenine moieties within A‐PPG micelles significantly increase selective endocytic uptake of the supramolecular micelles by cancer cells, which in turn induce apoptotic cell death and substantially enhance the response to chemotherapy. Thus, A‐PPG micelles can improve the safety and efficacy of cancer chemotherapy.

show abstract

Multifunctional adenine-functionalized supramolecular micelles for highly selective and effective cancer chemotherapy

Abstract: Adenine-functionalized supramolecular micelles are rapidly endocytosed by cancer cells and enable selective induction of tumor cell death, without harming normal cells.

Cited by 12 publications

References 44 publications

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

Functionalization of Polymers and Nanomaterials for Biomedical Applications: Antimicrobial Platforms and Drug Carriers

Adenine‐Functionalized Supramolecular Micelles for Selective Cancer Chemotherapy

Contact Info

Product

Resources

About