Diblock copolymers (PPDLx-b-pPAAy) were prepared from -pentadecalactone and L-glutamic acid or L-lysine amino acids by ring opening polymerization initiated by amino groups. Telechelic amino-ended poly(-pentadecalactone) with a length of 15-20 repeating units was firstly synthesized by enzymatic polymerization by means of CALB and then used as macroinitiator for the polymerization of the Ncarboxyanhydrides of the two -amino acids conveniently protected as benzyl and  Ncarbobenzoxy derivatives, respectively. The molecular weight of the polypeptide block was accurately controlled by adjusting the amino acid/macroinitiator ratio used in the feed. Copolymers with M n ranging between ~5000 and ~40,000 g•mol -1 and varying ester/peptide ratio were obtained and characterized in detail by GPC and NMR spectroscopy. The thermal properties of these copolymers were evaluated by TGA and DSC, and their structure in the solid-state including their response to heating, were examined by FTIR and XRD at variable temperature. It was shown that the polypentadecalactone segment was crystallized for all compositions and that the polypeptide counterpart adopted a two-dimensional hexagonal packing of -helices at temperatures above melting of the polyester block. SAXS revealed the presence of a biphasic nanostructure with a repeating distance of 27 nm for the case of glutamicbased copolymers. It was demonstrated that both glutamic and lysine-based PPDL x -b-pPAA y copolymers could self-assemble in well-shaped nanospheres with a diameter in the ~200-400 nm range and a negative zeta-potential. Highlights Polyester-polypeptide diblock copolymers are synthesized avoiding organo-metals. Both copolymer molecular weight and composition are well-controlled in the synthesis. In the solid state the copolymers have the two blocks separated and orderly arranged. The copolymers become self-assembled in water as spheres of 200-400 nm diameter. They are precursors for charged copolymers suited for stimuli-responsive biomaterials.

Polyglobalide (PGl) with number average polymerization degree of ~20 was prepared by enzymatic ROP and then polyfunctionalized at 60% with aminothioethylene groups. The PGl 20 -(NH 2 ) 12 copolymer was used as macroinitiator for the ROP of NCAs of BLG (-benzyl L-glutamate) and ZLL (  N-carbobenzoxy-L-lysine) protected amino acids to produce neutral polypeptide-grafted polyglobalides poly[Gl 20graft-(AA) z ] with z = 5 and 12, which upon deprotection, afforded anionic and cationic copolymers, respectively. Both protected and deprotected graft copolymers were characterized in full detail by NMR, and their thermal properties were evaluated by TGA and DSC. The structure of these copolymers in the solid-state was examined by FTIR and XRD using synchrotron radiation. All grafted polyglobalides were amorphous but the polypeptide side chains were arranged in either alpha-helix or beta-sheet conformation, and reliable indications on the occurrence of supramolecular structures were frequently found. The capacity of poly[Gl 20 -graft-(AA) z ] copolymers to selfassemble in aqueous medium was evidenced by the preparation of well-shaped spheroidal nanoparticles with a diversity of sizes depending on copolymer composition and charge. Loading and release of doxorubicin (DOX) from nanoparticles made of negatively charged poly[Gl 20 -graft-(LGA) 12 ] as well as DNA complexation with cationic poly[Gl 20 -graft-(LL) 5 ] were explored to appraise the potential of these copolymers for building drug delivery systems.

Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.

Metal-free catalysis was successfully applied to polymerize -pentadecalactone (PDL) by ring-opening polymerization (ROP) using several amino-ended initiators, namely hexylamine, allylamine and O,O′-bis(3-aminopropyl)diethylene glycol. This polymerization method was suitable to prepare telechelic polyesters carrying functional-end groups. The technique was then extended to the synthesis of block copolymers by ROP of PDL using bisamino-ended poly(ethylene glycol) (M n =2600) as macroinitiator. PPDL x-PEG 56-PPDL x triblock copolymers with M n ranging between ~4000 and ~90000 g•mol-1 were synthesized and extensively characterized by NMR, DSC, TGA and XRD. The amphiphilic copolymers thus produced were demonstrated to be able to self-assemble in nanoparticles with average diameters of ~100-200 nm and morphologies highly depending on blocks lengths. The described synthetic route distinguishes in providing "clean" amphiphilic copolymers, which are attractive candidates for biomedical applications.

Block and graft poly(macrolactone)‐poly(α‐amino acid) copolymers made of l‐alanine and pentadecalactone or globalide respectively, are prepared. A sequential ring‐opening polymerization (ROP) copolymerization route consisting of two stages, the first devoted to the preparation of the amino‐functionalized poly(macrolactone) and the second to the amino‐initiated polymerization of l‐alanine N‐carboxyanhydride (Ala‐NCA), is followed for the synthesis of both types of copolymers. Poly(l‐alanine) segment lengths are accurately controlled by adjusting the macroitiator/Ala‐NCA ratio used for reaction in the second stage. Block copolymers are semicrystalline with the poly(pentadecalactone) block crystallizes well in a separate phase and the poly(α‐amino acid) block arranged in either the α‐helical or β‐sheet structure in a ratio that is depending on composition and temperature. Graft copolymers are amorphous but with the poly(α‐amino acid) side chains arranged in a more or less regular conformation. Nanoparticles with a diameter of around 300 nm and moderate positive Z‐potential can be obtained from the block copolymers by self‐assembling in water whereas graft copolymers are unable to render recognizable objects of nanometer‐dimension under similar conditions.

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The enzymatic ring-opening copolymerization (eROP) of globalide (Gl) and pentadecalactone (PDL) was performed in solution from mixtures of the two macrolactones at ratios covering the whole range of comonomeric compositions. The resulting P(Glx-r-PDLy) random copolyesters were aminofunctionalized by thiol-ene reaction with aminoethanethiol. ROP of γ-benzyl-l-glutamate N-carboxyanhydride initiated by P(Glx-r-PDLy)-NH2 provided neutral poly(γ-benzyl-l-glutamate)-grafted copolyesters, which were converted by hydrolysis into negatively charged hybrid copolymers. Both water-soluble and nonsoluble copolymers were produced depending on copolymer charge and their grafting degree, and their capacity for self-assembling in nano-objects were comparatively examined. The emulsion solvent-evaporation technique applied to the chloroform-soluble copolymers grafted with benzyl glutamate rendered well-delineated spherical nanoparticles with an average diameter of 200–300 nm. Conversely, micellar solutions in water were produced from copolyesters bearing grafted chains composed of at least 10 units of glutamic acid in the free form. The copolymer micelles were shown to be able to load doxorubicin (DOX) efficiently through electrostatic interactions and also to release the drug at a rate that was markedly pH dependent.